AU2016259396A1 - Substituted triazoles useful as Axl inhibitors - Google Patents

Abstract

H:\rec\Interwoven\NRPortbl\DCC\REC\I2073840_I.docx-15/11/2016 Substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in -inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axn activity are also disclosed.

Description

SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of Australian Patent Application No. 2014200824, the entire content of which is incorporated herein by reference.

This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 60/988,352, filed November 15, 2007; U.S. Provisional Patent Application No. 60/883,713, filed January 5, 2007; and Provisional Patent Application No. 60/882,893, filed December 29, 2006, where these three provisional applications are incorporated herein by reference in their entireties.

FIELD OF THE INVENTION

This invention is directed to substituted triazoles and pharmaceutical compositions thereof which are useful as inhibitors of the receptor protein tyrosine kinase known as Axl. This invention is also directed to methods of using the compounds and compositions in treating diseases and conditions associated with Axl activity, particularly in treating diseases and conditions associated with angiogenesis and/or cell proliferation. BACKGROUND OF THE INVENTION

All of the protein kinases that have been identified to date in the human genome share a highly conserved catalytic domain of around 300 aa. This domain folds into a bilobed structure in which reside ATP-binding and catalytic sites. The complexity of protein kinase regulation allows many potential mechanisms of inhibition including competition with activating ligands, modulation of positive and negative regulators, interference with protein dimerization, and allosteric or competitive inhibition at the substrate or ATP binding sites.

Axl (also known as UFO, ARK, and Tyro7; nucleotide accession numbers NM_021913 and NM_001699; protein accession numbers NP_068713 and NP_001690) is a receptor protein tyrosine kinase (RTK) that comprises a C-terminal extracellular ligandbinding domain and N-terminal cytoplasmic region containing the catalytic domain. The extracellular domain of Axl has a unique structure that juxtaposes immunoglobulin and fibronectin Type III repeats and is reminiscent of the structure of neural cell adhesion molecules. Axl and its two close relatives, Mer / Nyk and Sky (Tyro3 / Rse / Dtk), collectively known as the Tyro3 family of RTK's, all bind and are stimulated to varying degrees by the same ligand, Gas6 (growth arrest specific-6), a ~76kDa secreted protein with significant homology to the coagulation cascade regulator, Protein S. In addition to binding to ligands, the Axl extracellular domain has been shown to undergo homophilic interactions that mediate cell aggregation, suggesting that one important function of Axl may be to mediate cell-cell adhesion.

Axl is predominantly expressed in the vasculature in both endothelial cells (EC’s) and vascular smooth muscle cells (VSMC’s) and in cells of the myeloid lineage and is also detected in breast epithelial cells, chondrocytes, Sertoli cells and neurons. Several functions including protection from apoptosis induced by serum starvation, TNF-α or the viral protein E1 A, as well as migration and cell differentiation have been ascribed to Axl signaling in cell culture. However, Axl-/- mice exhibit no overt developmental phenotype and the physiological function of Axl in vivo is not clearly established in the literature.

Angiogenesis (the formation of new blood vessels) Is limited to functions such as wound healing and the female reproductive cycle in healthy adults. This physiological process has been co-opted by tumors, thus securing an adequate blood supply that feeds tumor growth and facilitates metastasis. Deregulated angiogenesis also a feature of many other diseases (for example, psoriasis, rheumatoid arthritis, endometriosis and blindness due to age-related macular degeneration (AMD), retinopathy of prematurity and diabetes) and often contributes to the progression or pathology of the condition.

The overexpression of Axl and/or its ligand has also been reported in a wide variety of solid tumor types including, but not limited to, breast, renal, endometrial, ovarian, thyroid, non-small cell lung carcinoma, and uveal melanoma as well as in myeloid leukemia's. Furthermore, it possesses transforming activity in NIH3T3 and 32D cells. It has been demonstrated that loss of Axl expression In tumor cells blocks the growth of solid human neoplasms in an in vivo MDA-MB-231 breast carcinoma xenograft model. Taken together, these data suggest Axl signaling can independently regulate EC angiogenesis and tumor growth and thus represents a novel target class for tumor therapeutic development.

The expression of Axl and Gas6 proteins is upregulated in a variety of other disease states Including endometriosis, vascular injury and kidney disease and Axl signaling is functionally implicated in the latter two indications. Axl - Gas6 signaling amplifies platelet responses and is implicated in thrombus formation. Axl may thus potentially represent a therapeutic target for a number of diverse pathological conditions including solid tumors, including, but not limited to, breast, renal, endometrial, ovarian, thyroid, non-small cell lung carcinoma and uveal melanoma; liquid tumors, including but not limited to, leukemias (particularly myeloid leukemias) and lymphomas; endometriosis, vascular disease / injury (including but not limited to restenosis, atherosclerosis and thrombosis), psoriasis; visual impairment due to macular degeneration; diabetic retinopathy and retinopathy of prematurity; kidney disease (including but not limited to glomerulonephritis, diabetic nephropathy and renal transplant rejection), rheumatoid arthritis; osteoporosis, osteoarthritis and cataracts.

SUMMARY OF THE INVENTION

This invention is directed to certain substituted triazoles which are useful as Axl inhibitors, methods of using such compounds in treating diseases and conditions associated with Axl activity and pharmaceutical compositions comprising such compounds.

Accordingly, in one aspect this invention is directed to compounds of formula (I): (l) wherein:

R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(Re)R7; R2 is aryl optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-ORb, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-0-R10-C(0)N(R6)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-O-R10-N(R6)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(O)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R®-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)Rb, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R8)R7 (where t is 1 or 2); R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-Q-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R6)R7, -R9-O-R10-S(O)pR8 (where p isO, 1 or 2), -R9-O-R10-N(R®)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-Rb, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(P)N(R6)R7, -R9-N(R®)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R®-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R®)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or -OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.

In another aspect, this invention is directed to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of formula (I), as described above, as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.

In another aspect, this invention is directed to methods of treating a disease or condition associated with Axl activity in a mammal, wherein the methods comprise administering to the mammal a therapeutically effective amount of a compound of formula (I), as described above, as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (I), as described above, as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.

In another aspect, this invention provides assays to determine a compound of the invention effectiveness in inhibiting Axl activity in a cell-based assay.

DETAILED DESCRIPTION OF THE INVENTION DEFINITIONS

As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated: "Amino" refers to the -NH2 radical. "Carboxy" refers to the -C(0)0H radical. "Cyano" refers to the -CN radical. "Nitro" refers to the -N02 radical. "Oxa" refers to the -O- radical. "Oxo" refers to the =0 radical. "Thioxo" refers to the =S radical. "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to twelve carbon atoms, preferably one to eight carbon atoms or one to six carbon atoms ("lower alkyl"), and which is attached to the rest of the molecule by a single bond, for example, methyl, ethyl, /7-propyl, 1-methylethyl (/so-propyl), /7-butyl, /7-pentyl, 1,1-dimethylethyl (f-butyl), 3-methylhexyl, 2-methylhexyl, and the like. Unless stated otherwise specifically in the specification, an alkyl radical may be optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, -OR20, -OC(O)-RS0, -N(R20)2, -CiOJR20, -C(0)0R2°, -C(O)N(R20)2, -N(R20)C(O)OR20, -N(R20)C(O)R20, -N(R20)S(O),R20 (where t is 1 or 2), -S(0)tOR20 (where t is 1 or 2), -S(0)pR20 (where p is 0,1 or 2), and -S(O)tN(R20)2 (where t is 1 or 2) where each R20 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl. "Alkenyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one double bond, having from two to twelve carbon atoms, preferably one to eight carbon atoms and which is attached to the rest of the molecule by a single bond, for example, ethenyl, prop-1-enyl, but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless stated otherwise specifically in the specification, an alkenyl radical may be optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, -OR20, -0C(0)-R2°, -N(R20)2, -C(0)R20, -C(0)0R2°, -C(O)N(R20)2, -N(R20)C(O)OR20, -N(R20)C(O)R20, -N(R20)S(O)tR20 (where t is 1 or 2), -S(0)tOR20 (where t is 1 or 2), -S(0)pR20 (where p is 0,1 or 2), and -S(O)tN(R20)2 (where t is 1 or 2) where each R20 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl. "Alkynyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one triple bond, optionally containing at least one double bond, having from two to twelve carbon atoms, preferably one to eight carbon atoms and which is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise specifically in the specification, an alkynyl radical may be optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, -OR20, -OC(0)-R20, -N(R20)2, -C(0)R20, -C(0)0R2°, -C(O)N(R20)2, -N(R20)C(O)OR20, -N(R20)C(O)R20, -N(Rz0)S(O)tR20 (where t is 1 or 2), -S(0)t0R2° (where t is 1 or 2), -S(0)pR20 (where p is 0,1 or 2), and -S(O)tN(R20)2 (where t is 1 or 2) where each R20 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl. "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation and having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group can be through one carbon in the alkylene chain or through any two carbons within the chain. Unless stated otherwise specifically in the specification, an alkylene chain may be optionally substituted by one or more of the following substituents: halo, cyano, nitro, aryl, cycloalkyl, heterocyclyl, heteroaryl, oxo, thioxo, trimethylsilanyl, -OR20, -OC(0)-R20, -N(R20)2, -C(0)R20, -C(0)OR20, -C(O)N(R20)2, -N(Rz0)C(O)OR20, -N(R20)C(O)R20, -N(R20)S(O)tR20 (where t is 1 or 2), -S(0)t0R2° (where t is 1 or 2), -S(0)pR2° (where p is 0,1 or 2), and -S(O)tN(R20)2 (where t is 1 or 2) where each R20 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl. "Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one double bond and having from two to twelve carbon atoms, for example, ethenylene, propenylene, n-butenylene, and the like. The alkenylene chain is attached to the rest of the molecule through a double bond or a single bond and to the radical group through a double bond or a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group can be through one carbon or any two carbons within the chain. Unless stated otherwise specifically in the specification, an alkenylene chain may be optionally substituted by one or more of the following substituents: halo, cyano, nitro, aryl, cycloalkyl, heterocyclyl, heteroaryl, oxo, thioxo, trimethylsilanyl, -OR20, -OC(O)-Rz0, -N(R20)2, -C(O)Rz0, -C(0)0R2°, -C(O)N(R20)2, -N(R20)C(O)OR20, -N(R20)C(O)R20, -N(R20)S(O)tR20 (where t is 1 or 2), -SfOJtOR20 (where t is 1 or 2), -S(0)pR20 (where p is 0,1 or 2), and -S(O)tN(R20)2 (where t is 1 or 2) where each R20 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl. "Alkynylene" or "alkynylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one triple bond and having from two to twelve carbon atoms, for example, propynylene, n-butynylene, and the like. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a double bond or a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group can be through one carbon or any two carbons within the chain. Unless stated otherwise specifically in the specification, an alkynylene chain may be optionally substituted by one or more of the following substituents: alkyl, alkenyl, halo, haloalkenyl, cyano, nitro, aryl, cycloalkyl, heterocyclyl, heteroaryl, oxo, thioxo, trimethylsilanyl, -OR20, -0C(0)-R2°, -N(R20)2, -C(0)R20, -C(0)0R2°, -C(O)N(R20)z, -N(R20)C(O)OR20, -NiR^qOJR20, -N(R20)S(O),R20 (where t is 1 or 2), -S(0)t0R2° (where t is 1 or 2), -S(0)pR20 (where p is 0,1 or 2), and -S(O)tN(R20)2 (where t is 1 or 2) where each R20 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl. "Alkoxy” refers to a radical of the formula -ORa where Ra is an alkyl radical as defined above containing one to twelve carbon atoms. The alkyl part of the alkoxy radical may be optionally substituted as defined above for an alkyl radical. "Alkoxyalkyl" refers to a radical of the formula -Rb-O-Ra where 1¾ is an alkyl radical as defined above and Rb is an-alkylene chain as defined above. The oxygen atom may be bonded to any carbon in the alkyl radical or the alkylene chain. The alkyl part of the alkoxyalkyl radical may be optionally substituted as defined above for an alkyl radical and the alkylene chain part of the alkoxyalkyl radical may be optionally substituted as defined above for an alkylene chain. "Aryl" refers to a hydrocarbon ring system radical comprising hydrogen, 6 to 14 carbon atoms and at least one aromatic ring. For purposes of this invention, the aryl radical may be a monocyclic, bicyclic, or tricyclic system and which may include spiro ring systems. An aryl radical is commonly, but not necessarily, attached to the parent molecule via an aromatic ring of the aryl radical. For purposes of this invention, an "aryl" radical as defined herein can not contain rings having more than 7 members and cannot contain rings wherein two non-adjacent ring atoms thereof are connected through an atom or a group of atoms (/. e., a bridged ring system). Aryl radicals include, but are not limited to, aryl radicals derived from acenaphthylene, anthracene, azulene, benzene, 6,7,8,9-tetrahydro-5H-benzo[7]anniilene, fluorene, as-indaoene, s-indacene, indane, indene, naphthalene, phenalene, and phenanthrene. Unless stated otherwise specifically in the specification, the term "optionally substituted aryl" is meant to include aryl radicals optionally substituted by one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R21-OR20, -R21-0C(0)-R2°, -R21-N(R20)2, -R21-C(0)R20, -R21-C(0)0R2°, -R21-C(O)N(R20)2l -R21-O-R22-C(O)N(R20)2, -R21-N(R20)C(O)OR20, -R21-N(R20)C(O)R20, -R21-N(R20)S(O)tR20 (where t is 1 or 2), -R21-S(0),OR20 (where t is 1 or 2), -R21-S(0)pR2° (where p is 0,1 or 2), and -R21-S(O)tN(R20)2 (where t is 1 or 2), where each R20 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl, or two R20's, together with the common nitrogen to which they are both attached, may optionally form an optionally substituted W-heterocyclyl or an optionally substituted /V-heteroaryl, each R21 is Independently a direct bond or a straight or branched alkylene or alkenylene chain, and R22 is a straight or branched alkylene or alkenylene chain. "Aralkyl" refers to a radical of the formula -Rd-Rc where Rb is an alkylene chain as defined above and Rc is one or more aryl radicals as defined above, for example, benzyl, diphenylmethyl and the like. The alkylene chain part of the aralkyl radical may be optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical may be optionally substituted as described above for an aryl. "Aralkenyl" refers to a radical of the formula -Rd-Rc where Rd is an alkenylene chain as defined above and Rc is one or more aryl radicals as defined above. The aryl part of the aralkenyl radical may be optionally substituted as described above for an aryl. The alkenylene chain part of the aralkenyl radical may be optionally substituted as defined above for an alkenylene group. "Aralkynyl" refers to a radical of the formula -ReRc where Re is an alkynylene chain as defined above and Rc is one or more aryl radicals as defined above. The aryl part of the aralkynyl radical may be optionally substituted as described above for an aryl. The alkynylene chain part of the aralkynyl radical may be optionally substituted as defined above for an alkynylene chain. "Aryloxy" refers to a radical of the formula -OR0 where R0 is an aryl as defined above. The aryl part of the aryloxy radical may be optionally substituted as defined above. "Aralkyloxy" refers to a radical of the formula -ORf where Rf is an aralkyl radical as defined above. The aralkyl part of the aralkyloxy radical may be optionally substituted as defined above. "Cycloalkyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which may include spiro or bridged ring systems, having from three to fifteen carbon atoms, preferably having from three to ten carbon atoms, more preferably from five to seven carbons and which is saturated or unsaturated and attached to the rest of the molecule by a single bond. For purposes of this invention, a bridged ring system is a system wherein two non-adjacent ring atoms thereof are connected through an atom or a group of atoms. Monocyclic cycloalkyl radicals Include non-bridged cycloalkyl radicals, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic radicals include fused, spiro or bridged cycloalkyl radicals, for example, C10 radicals such as adamantanyl (bridged) and decalinyl (fused), and C7 radicals such as bicyclo[3.2.0]heptanyl (fused), norbornanyl and norbornenyl (bridged), as well as substituted polycyclic radicals, for example, substituted C7 radicals such as 7,7-dimethylbicyclo[2.2.1]heptanyl (bridged), and the like. Unless otherwise stated specifically in the specification, cycloalkyl radicals defined herein may be "optionally substituted" by one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkynyl, oxo, thioxo, cyano, nltro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocydylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R21-OR20, -R21-0C(0)-R2°, -R21-N(R20)2, -R21-C(0)R2°, -R21-C(0)0R2°, -R21-C(O)N(R20)2, -R21-N(R20)C(O)OR20, -R21-N(R20)C(O)R20, -R21-N(R20)S(O)tR20 (where t is 1 or 2), -R21-S(0)t0R2° (where t is 1 or 2), -R21-S(O)pRz0 (where p is 0,1 or 2), and -R21-S(O)tN(R20)2 (where t is 1 or 2), where each R20 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl, or two R20's, together with the common nitrogen to which they are both attached, may optionally form an optionally substituted /V-heterocyclyl or an optionally substituted /V-heteroaryl, and each R21 is independently a direct bond or a straight or branched alkylene or alkenylene chain. "Cycloalkylalkyr refers to a radical of the formula -RbRg where Rb is an alkylene chain as defined above and Rg is a cycloalkyl radical as defined above. The alkylene chain and the cycloalkyl radical may be optionally substituted as defined above. "Cycloalkylalkenyl" refers to a radical of the formula -RdRg where Rd is an alkenylene chain as defined above and Rg is a cycloalkyl radical as defined above. The alkenylene chain and the cycloalkyl radical may be optionally substituted as defined above. "Cycloalkylalkynyl" refers to a radical of the formula -ReRg where Re is an alkynylene radical as defined above and Rg is a cycloalkyl radical as defined above. The alkynylene chain and the cycloalkyi radical may be optionally substituted as defined above. "Halo" refers to bromo, chloro, fluoro or iodo. "Haloalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, for example, trifluoromethyl, difluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, 3-bromo-2-fluoropropyl, 1-bromomethyl-2-bromoethyl, and the like. The alkyl part of the haloalkyl radical may be optionally substituted as defined above for an alkyl radical. "Haloalkoxy" refers to an alkoxy radical, as defined above, that is substituted by one or more halo radicals, as defined above, for example, trifluoromethoxy, difluoromethoxy, trichloromethoxy, 2,2,2-trifluoroethoxy, and the like. The alkoxy part of the haloalkoxy radical may be optionally substituted as defined above for an alkoxy radical. "Haloalkenyl" refers to an alkenyl radical, as defined above, that is substituted by one or more halo radicals, as defined above. The alkenyl part of the haloalkyl radical may be optionally substituted as defined above for an alkenyl radical. "Haloalkynyl" refers to an alkynyl radical, as defined above, that is substituted by one or more halo radicals, as defined above. The alkynyl part of the haloalkyl radical may be optionally substituted as defined above for an alkynyl radical. "Heterocyclyr refers to a stable 3- to 18-membered non-aromatic ring radical which comprises one to twelve carbon atoms and from one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. Unless stated otherwise specifically in the specification, the heterocyclyl radical may be a monocyclic, bicydic, tricyclic or tetracyclic ring system, which may include spiro or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heterocyclyl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized; and the heterocyclyl radical may be partially or fully saturated. Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, 1,4-diazepanyl, decahydroisoquinolyl, imidazoiinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, octahydro-1H-pyrrolo[3,2-c]pyridinyl, octahydro-1 /-/-pyrrolo[2,3-c]pyridinyl, octahydro-1 H-pyrrolo[2,3-b]pyridinyl, octahydro-1 W-pyrrolo[3,4-b]pyridinyl, octahydropyrrolo[3,4-c]pyrrolyl, octahydro-1 /+pyrido[1,2-a]pyrazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyi, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuranyl, thienyl[1,3]dithianyl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, azetidinyl, octahydropyrrolo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-b]pyrrolyl, decahydroprazino[1,2-a]azepinyl, azepanyl, azabicyclo[3.2.1]octyl, and 2,7-diazaspiro[4.4]nonanyl. Unless stated otherwise specifically in the specification, the term ” optionally substituted heterocyclyi" is meant to include heterocyclyl radicals as defined above which are optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkynyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R21-OR20, -R21-0C(0)-R2°, -R21-N(R20)2, -R21-C(0)R2°, -R21-C(0)0R2°, -R21-C(O)N(Rz0)2, -R21-N(R20)C(O)OR20, -R21-N(R20)C(O)R20, -R21-N(R20)S(O)tR20 (where t is 1 or 2), -R21-S(0)t0R2° (where t is 1 or 2), -R21-S(0)pR2° (where p is 0,1 or 2), and -R21-S(O)tN(R20)2 (where t is 1 or 2), where each R20 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl, or two R20’s, together with the common nitrogen to which they are both attached, may optionally form an optionally substituted N· heterocyclyl or an optionally substituted N-heteroaryl, and each R21 is independently a direct bond or a straight or branched alkylene or alkenylene chain. "A/-heterocyclyl" refers to a heterocyclyl radical as defined above containing at least one nitrogen and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a nitrogen atom In the heterocyclyl radical. An A/-heterocyclyl radical may be optionally substituted as described above for heterocyclyl radicals. "Heterocyclylalkyl" refers to a radical of the formula -RbRh where Rb is an alkylene chain as defined above and Rh is a heterocyclyl radical as defined above, and If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl may be attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkyl radical may be optionally substituted as defined above for an alkylene chain. The heterocyclyl part of the heterocyclylalkyl radical may be optionally substituted as defined above for a heterocyclyl radical. "Heterocydylalkenyl" refers to a radical of the formula -R<jRh where R<j is an alkenylene chain as defined above and Rh is a heterocyclyl radical as defined above, and if the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl may be attached to the alkenylene chain at the nitrogen atom. The alkenylene chain of the heterocydylalkenyl radical may be optionally substituted as defined above for an alkenylene chain. The heterocyclyl part of the heterocydylalkenyl radical may be optionally substituted as defined above for a heterocyclyl radical. "Heterocydylalkynyl" refers to a radical of the formula -ReRh where Re is an alkynylene chain as defined above and Rh is a heterocyclyl radical as defined above, and if the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl may be attached to the alkynyl radical at the nitrogen atom. The alkynylene chain part of the heterocydylalkynyl radical may be optionally substituted as defined above for an alkynylene chain. The heterocyclyl part of the heterocydylalkynyl radical may be optionally substituted as defined above for a heterocyclyl radical. "Heteroaryl" refers to a 5- to 14-membered ring system radical comprising hydrogen atoms, one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and at least one aromatic ring. A heteroaryl radical is commonly, but not necessarily, attached to the parent molecule via an aromatic ring of the heteroaryl radical. For purposes of this invention, the heteroaryl radical may be a monocyclic, bicyclic or tricyclic ring system, which may include spIro ring systems; and the nitrogen, carbon or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized. For purposes of this invention, the aromatic ring of the heteroaryl radical need not contain a heteroatom, as long as one ring of the heteroaryl radical contains a heteroatom. For example, 1,2,3,4-tetrahydroisoquinolin-7-yl is considered a "heteroaryl" for the purposes of this invention. For purposes of this invention, a "heteroaryl" radical as defined herein can not contain rings having more than 7 members and cannot contain rings wherein two non-adjacent ring atoms thereof are connected through an atom or a group of atoms (i.e., a bridged ring system). Examples of heteroaryl radicals include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzo[d]imidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[/b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2-d|pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, chromeno[4,3-c]pyridazinyl, cinnolinyl, cyclopenta[c/|pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-of|pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5.6- dihydrobenzo[h]cinnolinyl, 7',8,-dihydro-5'A/-spiro[[1,3]dioxolane-2,6,-quinoline]-3,-yl, 6.7- dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, furopyrimidinyl, furopyridazinyl, furopyrazinyl, isothiazolyl, imidazolyl, imidazopyrimidinyl, imidazopyridazinyl, imidazopyrazinyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolinyl (isoquinolyl), indolizinyl, isoxazolyl, naphthyridinyl, naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzothjquinazolinyl, 1-phenyl-1 W-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, phenanthridinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-c/|pyrimidinyl, pyridinyl (pyridyl), pyrido[3,2-cf|pyrimidinyl, pyrido[3,4-c(|pyrirnidinyl, pyrido[4,3-c]pyridazinyl, pyrazinyl, pyrimidinyl, pyridazinyl (pyridazyl), pyrrolyl, pyrrolopyrimidinyl, pyrrolopyridazinyl, pyrrolopyrazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 2,3,4,5-tetrahydrobenzo[£)]oxepiny1, 3,4-dihydro-2/-/-benzo[fo][1,4]dioxepinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinyl, 6,7,8,9-tetrahydro-5H-pyrido[3,2-c]azepinyl, 5.6.7.8- tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6.7.8.9- tetrahydro-5H-cyclohepta[4,5]thieno[2,3-c/]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, 1,2,3,4-tetrahydroisoquinolin-7-yl, triazinyl, thieno[2,3-d]pyrimidinyl, thienopyrimidinyl (e.g., thieno[3,2-c/Jpyrimidinyl or thieno[2,3-c/]pyrimidinyl), thieno[2,3-c]pyridinyl, thienopyridazinyl, thienopyrazinyl, and thiophenyl (thienyl). Unless stated otherwise specifically in the specification, the term " optionally substituted heteroaryl” is meant to include heteroaryl radicals as defined above which are optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkynyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R21-OR20, -R21-0C(0)-R2°, -R21-N(R20)2, -R21-C(0)R2°, -R21-C(0)0R2°, -R21-C(O)N(R20)2, -R21-N(R20)C(O)OR20, -R21-N(R20)C(O)R20, -R21-N(R20)S(O)tR20 (where t is 1 or 2), -R21-S(0),0R2° (where t is 1 or 2), -R21-S(0)pR2° (where p is 0,1 or 2), and -R21-S(O)tN(R20)2 (where t is 1 or 2), where each R20 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl, or two R20,s, together with the common nitrogen to which they are both attached, may optionally form an optionally substituted N-heterocyclyl or an optionally substituted AAheteroaryl, and each R21 is independently a direct bond or a straight or branched alkylene or alkenylene chain. "W-heteroaryl" refers to a heteroaryl radical as defined above containing at least one nitrogen and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a nitrogen atom in the heteroaryl radical. An W-heteroaryl radical may be optionally substituted as described above for heteroaryl radicals, "Heteroarylalkyl" refers to a radical of the formula -RbRi where 1¾ is an alkylene chain as defined above and Ri is a heteroaryl radical as defined above. The heteroaryl part of the heteroarylalkyl radical may be optionally substituted as defined above for a heteroaryl. The alkylene chain part of the heteroarylalkyl radical may be optionally substituted as defined above for an alkylene chain. "Heteroarylalkenyl" refers to a radical of the formula -RjRi where Rd Is an alkenylene chain as defined above and R is a heteroaryl radical as defined above. The heteroaryl part of the heteroarylalkenyl radical may be optionally substituted as defined above for a heteroaryl. The alkenylene chain part of the heteroarylalkenyl radical may be optionally substituted as defined above for an alkenylene chain. "Heteroarylalkynyl" refers to a radical of the formula -R,R where Re is an alkynylene chain as defined above and R is a heteroaryl radical as defined above. The heteroaryl part of the heteroarylalkynyl radical may be optionally substituted as defined above for a heteroaryl. The alkynylene chain part of the heteroarylalkynyl radical may be optionally substituted as defined above for an alkynylene chain. "Hydroxyalkyl" refers to an alkyl radical as defined above which is substituted by one or more hydroxy radicals (-OH). "Hydroxyalkenyl" refers to an alkenyl radical as defined above which is substituted by one or more hydroxy radicals (-OH). "Hydroxyalkenyl" refers to an alkynyl radical as defined above which is substituted by one or more hydroxy radicals (-OH).

Certain chemical groups named herein may be preceded by a shorthand notation indicating the total number of carbon atoms that are to be found in the indicated chemical group. For example; C7-Ci2alkyl describes an alkyl group, as defined below, having a total of 7 to 12 carbon atoms, and C4-Ci2cycloalkylalkyl describes a cycloalkylalkyl group, as defined below, having a total of 4 to 12 carbon atoms. The total number of carbons in the shorthand notation does not include carbons that may exist in substituents of the group described. "Stable compound" and "stable structure" are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. "Mammal" includes humans and domestic animals, such as cats, dogs, swine, cattle, sheep, goats, horses, rabbits, and the like. Preferably, for purposes of this invention, the mammal is a human. "Optional" or "optionally" means that the subsequently described event or circumstances may or may not occur, and that the description includes Instances where said event or circumstance occurs and instances in which it does not. For example, "optionally substituted aryl" means that the aryl radical may or may not be substituted and that the description includes both substituted aryl radicals and aryl radicals having no substitution. When a functional group is described as "optionally substituted," and in turn, substitutents on the functional group are also "optionally substituted" and so on, for the purposes of this invention, such iterations are limited to five, preferably such iterations are limited to two. "Pharmaceutically acceptable excipient" includes without limitation any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye/colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier which has been approved by the United States Food and Drug Administration as being acceptable for use in humans or domestic animals. "Pharmaceutically acceptable salt" includes both acid and base addition salts. "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfonic acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuricacid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfinic acid, trifluoroacetic acid, undecylenic acid, and the like. "Pharmaceutically acceptable base addition salt” refers to those salts which retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Preferred inorganic salts are the ammonium, sodium, potassium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benethamine, benzathine, ethylenediamine, glucosamine, methylglucamine, theobromine, triethanolamine, tromethamine, purines, piperazine, piperidine, /V-ethylpiperidine, polyamine resins and the like. Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline and caffeine. A "pharmaceutical composition" refers to a formulation of a compound of the invention and a medium generally accepted in the art for the delivery of the biologically active compound to mammals, for example, humans. Such a medium includes all pharmaceutically acceptable carriers, diluents or excipients therefor. "Therapeutically effective amount" refers to that amount of a compound of the invention which, when administered to a mammal, preferably a human, is sufficient to effect treatment, as defined below, of a disease or condition of interest in the mammal, preferably a human. The amount of a compound of the invention which constitutes a "therapeutically effective amount" will vary depending on the compound, the disease or condition and its severity, and the age of the mammal to be treated, but can be determined routinely by one of ordinary skill in the art having regard to his own knowledge and to this disclosure. "Treating" or "treatment" as used herein covers the treatment of the disease or condition of interest in a mammal, preferably a human, having the disease or condition of interest, and includes: (i) preventing the disease or condition from occurring in a mammal, in particular, when such mammal Is predisposed to the condition but has not yet been diagnosed as having it; (ii) inhibiting the disease or condition, /.e., arresting its development; (iii) relieving the disease or condition, I.e., causing regression of the disease or condition; or (iv) stabilizing the disease or condition.

As used herein, the terms "disease" and "condition" may be used interchangeably or may be different in that the particular malady or condition may not have a known causative agent (so that etiology has not yet been worked out) and it is therefore not yet recognized as a disease but only as an undesirable condition or syndrome, wherein a more or less specific set of symptoms have been identified by clinicians.

The compounds of the invention, or their pharmaceutically acceptable salts may contain one or more asymmetric centres and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)- or, as (D)- or (L)- for amino acids. The present invention is meant to include all such possible isomers, as well as their racemic and optically pure forms. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques, such as HPLC using a chiral column. When the compounds described herein contain olefinic double bonds or other centres of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers. Likewise, all tautomeric forms are also intended to be included. A "stereoisomer" refers to a compound made up of the same atoms bonded by the same bonds but having different three-dimensional structures, which are not interchangeable. The present invention contemplates various stereoisomers and mixtures thereof and includes "enantiomers", which refers to two stereoisomers whose molecules are nonsuperimposeable mirror images of one another. A "tautomer” refers to a proton shift from one atom of a molecule to another atom of the same molecule. The present invention includes tautomers of any said compounds. "Atropisomers” are stereoisomers resulting from hindered rotation about single bonds where the barrier to rotation is high enough to allow for the isolation of the conformers (Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley &amp; Sons: New York, 1994; Chapter 14). Atropisomerism is significant because it introduces an element of chirality in the absence of stereogenic atoms. The invention is meant to encompass atropisomers, for example in cases of limited rotation around the single bonds emanating from the core triazole structure, atropisomers are also possible and are also specifically included in the compounds of the invention.

The chemical naming protocol and structure diagrams used herein are a modified form of the I.U.P.A.C. nomenclature system wherein the compounds of the invention are named herein as derivatives of the central core structure, i.e., the triazole structure. For complex chemical names employed herein, a substituent group is named before the group to which it attaches. For example, cyclopropylethyl comprises an ethyl backbone with cyclopropyl substituent. In chemical structure diagrams, all bonds are identified, except for some carbon atoms, which are assumed to be bonded to sufficient hydrogen atoms to complete the valency.

For purposes of this invention, the depiction of the bond attaching the R3 substituent to the parent triazole moiety in formula (I), as shown below:

(I) t is intended to include only the two regioisomers shown below, i.e., compounds of formula (la) and (lb):

The numbering system of the ring atoms in compounds of formula (la) is shown below:

For example, a compound of formula (la) wherein R1, R4 and R5 are each hydrogen, R2 is 4-(4-((1 S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl and R3 is 2-chloro-7-methylthieno[3,2-£/]pyrimidin-4-yl; i.e., a compound of the following formula:

is named herein as /^-(4-(4-(( 1 S12S,4R)-bicyclot2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)- 1-(2-chloro-7-methylthieno[3,2-c/]pyrimidin-4-yl)-1/-/-1,2,4-triazole-3,5-diamine.

The numbering system of the ring atoms in compounds of formula (lb) is shown below:

For example, a compound of formula (lb) wherein R1, R4 and R5 are each hydrogen, R2 is 4-(4-cyclohexylpiperazin-1-yl)phenyl and R3 is 6,7-dimethoxyquinazolin- 4-yl; i.e., a compound of the following formula:

is named herein as W5-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazole-3,5-diamine.

EMBODIMENTS OF THE INVENTION

Of the various aspects of the compounds of formula (I), as set forth above in the Summary of the Invention, certain embodiments are preferred.

Accordingly, one embodiment of the compounds of formula (I), as set forth above in the Summary of the Invention, is wherein the compound of formula (I) is a compound of formula (la):

wherein: R1, R4 and R® are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(Re)R7; R2 is aryl optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R8)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-O-R10-N(R8)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)Rb, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R6)R7, -R9-O-R10-S(O)pR8 (where p is 0, 1 or 2), -R9-O-R10-N(R8)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)Rs, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(Rb)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t Is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R8)R7 (where t Is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or-OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.

One embodiment of the compounds of formula (la), as set forth above, is a compound of formula (la) which is a compound of formula (Ia1):

(Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; r23 !s -R10a-N(R6a)R7a where R6® and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R28 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R99-OR89, -R99-C(0)R8fl, -R"-C(0)0R89, -R^NfR^JR79 and -R99-C(0)N(R69)R7g, where each R60, R70 and R8® is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R90 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkyialkyt, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R8)R7, -R9-O-R10-S(O)pR8 (where p is 0, 1 or 2), -R9-O-R10-N(Re)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Rs)R7, -R9-N(Re)C(0)0R8, -R9-N(Rs)C(0)R8, -R9-N(Re)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cydoalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -r10-C(O)OR® and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cydoalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or -OR®.

One embodiment of the compounds of formula (Ia1), as set forth above, is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R99-OR8g, -R"-C(0)R89, -R"-C(0)0R89, -R99-N(R80)R7s and -R99-C(0)N(R69)R79, where each R89, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0)tR8 (where t is 1 or 2), -R^O^OR8 (where t is 1 or 2), -R9-S(0)pR® (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia1), as set forth above, is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2ais -R10a-N(R6a)R7a where R®a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted Af-heteroaryl or an optionally substituted A/-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R99-C(0)R8s, -R99-C(0)0R89, -R99-N(R69)R70 and -R99-C(0)N(R89)R79, where each R69, R79 and R89 Is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R®9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 Is a monocyclic aryl optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)RB, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)Rb, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tlM(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R^-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -^°-0(0)ΙΜ^)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein RZa is selected from the group consisting of optionally substituted 2-(piperidinyl)ethyl and optionally substituted 2-(pyrrolidinyl)ethyl and R3 is optionally substituted phenyl.

One embodiment of this preferred embodiment is a compound of formula (Ia1), as set forth above, selected from the group consisting of: 1-phenyl-/V3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(4-isopropylphenyl)-A/3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; 4-(5-amino-3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenylamino)-1 H-1,2,4-triazol-1 -yl)benzenesulfonamide; 1-(2-fluorophenyl)-A/3-(4-(2-(2-methylpyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2>4-triazole-3,5- diamine; 1 -(2-fluorophenyi)-/V3-(4-(2-(piperidin-1 -yl )ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; and 1-(2-fluorophenyl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia1), as set forth above, is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a Is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R"-C(0)R89, -R99-C(0)0R89, -R"-N(R09)R79 and -R99-C(0)N(R69)R79, where each R®9, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R" is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 Is a monocyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R®-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(Re)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 Is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R2a is selected from the group consisting of optionally substituted 2-(piperidinyl)ethyl and optionally substituted 2-(pyrrolidinyl)ethyl and R3 Is selected from the group consisting of optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyridazinyl and optionally substituted pyrazinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia1), as set forth above, selected from the group consisting of: /V3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(pyridin-2-yl)-1H-1,2,4-triazole-3,5- diamine; 1-(pyridin-2-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; A/5-methyl-1-(pyridin-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(4-(trifluoromethyl)pyrimidin-2-yl )-1/-/-1,2,4-triazole-3,5-diamine; 1-(2-chloropyridin-4-yl)-/V3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5- diamine; 1-(6-chloropyridazin-3-yl)-W3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1I2,4-triazole-3,5- diamine; 1-(pyrazi n-2-yl)-/\/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1 -(2-morpholinopyridin-4-yl)-/V3-(4-(2-(piperidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6-chloropyridin-2-yl)-W3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5- diamine; 1-(5-chloropyridin-2-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5- diamine; 1 -(3-chloropyridin-2-yl)-/V3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6-chloropyridin-2-yl)-/\/3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3I5- diamine; 1-(6-morpholinopyridin-2-yl)-/V3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5- diamine; N3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 -(4-(trifluoromethyl)pyridin-2-yl)-1 H-1,2,4-triazole-3,5-diamine; /^-( 4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(3-(trifluoromethyl)pyridin-2-yl)-1W-1,2,4-triazole-3,5-diamine; 1 -(6-methoxypyridin-2-yl)-/V3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1 -(5-bromopy ridi n-2-yl )-/^-(4-( 2-( pyrrolidi n-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-dlamine; 1-(6-(methylamino)pyridin-2-yl)-/V3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole- 3,5-diamine; 1- (6-(dimethylamino)pyridin-2-yl)-W3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4- triazole-3,5-diamine; 2- (5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-lW-1,2,4-triazol-1-yl)-6- methylpyrimidin-4-ol; 1-( pyrimidin-2-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl )-1 W-1,2,4-triazole-3,5-diamine; and /V3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(pyridin-2-yl)-1W-1,2,4-triazole-3,5- diamine.

Another embodiment of the compounds of formula (Ia1) is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZais -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R"-C(0)R89, -R"-C(0)0R89, -R®9-N(R69)R79 and -R99-C(0)N(R89)R79, where each R69, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R®9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R®-OR8, -R®-0C(0)-R8, -R®-N(R6)R7, -R®-C(0)R8, -R®-C(0)0R8, -R®-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia1) is a compound of formula (Ia1) wherein: R\ R4 and R® are each independently selected from the group consisting of hydrogen and alkyl; R2ais -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R99-OR89, -R"-C(0)R89, -R"-C(0)0R89, -R9g-N(R69)R7fl and -R"-C(0)N(R69)R79, where each R69, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a bicyclic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0Rb, -R9-N(R8)C(0)R8, -R9-N(R6)S(0),Rb (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted h eterocycl y I a Ikyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia1) is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZa is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /7-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R"-C(0)R89, -R^CiOJOR89, -R"-N(R®9)R79 and -R^qOMR®9^79, where each R®9, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R" is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a bicyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R®)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R2a is optionally substituted 2-(pyrrolidinyl)ethyl and R3 is selected from the group consisting of optionally substituted quinazolinyl, optionally substituted quinoxalinyl, optionally substituted benzo[d]thiazolyl, optionally substituted benzo[d]imidazolyl, optionally substituted phthalazinyl, optionally substituted isoquinolinyl, optionally substituted thieno[2,3-c]pyridinyl, optionally substituted furo[3,2-c]pyridinyl, optionally substituted tetrahydroquinazolinyl, optionally substituted naphthyridinonyl, optionally substituted pyrido[4,3-c]pyridazinyl, optionally substituted thieno[2,3-d]pyrimidinyl and optionally substituted thieno[3,2-d]pyrimidinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia1), as set forth above, selected from the group consisting of: 1 -(7-(benzyloxy)-6-methoxyquinazolin-4-yl)-A/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H- 1,2,4-triazole-3,5-diamine; /V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(quinoxalin-2-yl)-1W-1,2,4-triazole-3,5-diamine; 1 -(benzo[d]thiazol-2-yl )-/^-( 4-(2-( py rrolidi n-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(1-methyl-1 H-benzo[d]imidazol-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl )-1/7-1,2,4-triazole-3,5-diamine; /S/3-(4-(2-(2-methylpyrrolidin-1 -yl)ethoxy)phenyl)-1 -(quinoxalin-2-yl)-1 /7-1,2,4-triazole-3,5-diamine; 1 -(benzo[c/Jthiazol-2-yl)-/V3-(4-(2-(2-methylpyrrolidin-1 -yl)ethoxy)phenyl)-1 /7-1,2,4-triazole-3,5-diamine; 1-(1-methyl-1/7-benzo[d]imidazol-2-yl)-A/3-(4-(2-(2-methylpyrrolidin-1-y|)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(1 /7-benzo[c/Jimidazol-2-yl)-/\/3-(4-(2-(2-methylpyrrolidin-1 -yl)ethoxy)phenyl)-1 /7-1,2,4-triazole-3,5-diamine; 1-(phthalazin-1-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1/7-1,2,4-triazole-3,5-diamine; 1-(1H-benzo[c/limidazol-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole- 3.5- diamine; methyl 1-(2-(4-(5-amino-1-(quinoxalin-2-yl)-1H-1,2,4-triazol-3-ylamino)phenoxy)ethyl)pyrrolidine-2-carboxylate; 1-(2-chloroquinazolin-4-yl )-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl )-1/-/-1,2,4-triazole-3,5-diamine; 1-(2-morpholinoquinazolin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1/-/-1,2,4-triazole- 3.5- diamine; 1-(benzo[cdthiazol-2-yl)-/\/3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; A/3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(1-methyl-1/-/-benzo[c/]imidazol-2-yl)-1H-1,2,4-triazole-3,5-diamine; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(quinolin-2-yl)-1H-1,2,4-triazole-3,5-diamine; methyl 1 -(2-(4-(5-amino-1 -(benzo[c/]thiazol-2-yl)-1 H-1,2,4-triazol-3-ylamino)phenoxy)ethyl)pyrrolidine-2-carboxylate; 1-(2-chloro-6,7-dimethoxyquinazolin-4-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H- 1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyquinazolin-4-yl)-/\/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; /^-( 4-(2-(2,5-dimethylpyrrolidin-1-yl)ethoxy)phenyl)-1-(quinoxalin-2-yl )-1 H-1,2,4-triazole- 3.5- diamine; 1 -(6-chloroquinazolin-4-yl)-A/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(2-chloro-6,7-dihydro-5H-cyclopenta[c/]pyrimidin-4-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(isoquinoiin-1-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl )-1 H-1,2,4-triazole-3,5-diamine; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(thieno[2,3-cdpyrimidin-4-yl)-1 H-1,2,4-triazole- 3.5- diamine; 1-(6-phenylthieno[3,2-c/lpyrimidin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(2-(trifluoromethyl)quinazolin-4-yl)-1H-1,2,4- triazole-3,5-diamine; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(thieno[3,2-c/lpyrimidin-4-yl)-1H-1,2,4-triazole- 3.5- diamine; /\/3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(quinoxalin-2-yl)-1/-/-1,2,4-triazole-3,5- diamine; 1-(benzo[cdthiazol-2-yl)-/\/3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(2-chloro-7-methylthieno[3,2-(/lpyrimidin-4-yl)-/\/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5-diamine; /\/3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(isoquinolin-1-yl)-1W-1,2,4-triazole-3,5- diamine; A/3-(3-chloro-4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 -(6,7-dimethoxyquinazolin-4-yl)-1 H- 1.2.4- triazole-3,5-diamine; A/3-(3-chloro-4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 -(isoquinolin-1 -yl)-1 H-1,2,4-triazole-3,5-diamine; 1 -(6-fluoroquinazolin-4-yl)-/\/3-(4-(2-(pyriOlidin-1 -yl)ethoxy)phenyl)-1 W-1,2,4-triazole-3,5-diamine; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(thieno[2,3-c]pyridin-7-yl)-1W-1,2,4-triazole-3,5- diamine; 1-(2-methylquinazolin-4-yl)-/\/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5- diamine; 1- (furo[3,2-c]pyridin-4-yl)-W3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5- diamine; 2- (5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1H-1,2,4-triazol-1-yl)-5,6,7,8- tetrahydroquinazolin-4-ol; 1-(6,7-dimethoxyisoquinolin-1-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5-diamine; 5-(5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1W-1,2,4-triazol-1-yl)-1,6-naphthyridin-2( 1H)-one; benzyl 3-(5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1AV-1,2,4-triazol-1-yl)-7,8-dihydropyrido[4,3-c]pyridazine-6(5H)-carboxylate; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(5,6,7,8-tetrahydropyrido[4,3-c]pyridazin-3-yl)-1/-/-1,2,4-triazole-3,5-diamine; 1 -(2,6-dichlorothieno[3,2-o(lpyrimidin-4-yl)-/V3-(4-(2-pyrrolidin-1 -ylethoxy)phenyl)-1 H- 1.2.4- triazole-3,5-diamine; 1-(2-chlorothieno[2,3-c(lpyrimidin-4-yl)-A/3-(4-(2-pyrrolidin-1-ylethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; and 1-(2-chlorothieno[3,2-odpyrimidin-4-yl)-/\/3-(4-(2-pyrrolidin-1-ylethoxy)phenyl)-1H-1,2,4- triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia1) is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a js .R10a-N(R6a)R7a where R6a and R70, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R"-C(0)R89, -R99-C(0)0R89, -R"-N(R69)R79 and -R"-C(0)N(R69)R79, where each R89, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)Rb, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R8)C(0)0R8, -Rb-N(R6)C(0)R8, -R9-N(R8)S(0)|R8 (where t is 1 or 2), -R0-S(O)|OR8 (where t is 1 or 2), -R®-S(0)pR8 (where p is 0,1 or 2), and -R0-S(O),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia1) is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where Rea and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R20 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR80, -R9fl-C(0)R8g, -R9fl-C(0)0R8e, -R99-N(R60)R70 and -R"-C(O)N(R80)R79, where each R80, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R" is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a tricyclic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyciylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(Re)R7, -R^CfOJR8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R8)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R8)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyi, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyi, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia1) is a compound of formula (Ia1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R99-OR89, -R"-C(0)R89, -R9b-C(0)0R89, -R’fc-NiR^R79 and -R"-C(0)N(R89)R79, where each R®9, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9fl is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a tricyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R®)C(0)R8, -R9-N(R®)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R®)R7 (where t is 1 or 2); each R8 and R7 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment Is wherein RZa is optionally substituted 2-(pyrrolidinyl)ethyl and R3 Is selected from the group consisting of optionally substituted 5,6,6a,7,8,9,10,10a-octahydrobenzo[/7]quinazolinyl, optionally substituted 5,6-dihydrobenzo[/?]quinazollnyl, optionally substituted 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-c/]pyrimidinyl, optionally substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-c/]pyrimidinyl, optionally substituted phthalazinyl, optionally substituted 6,7-dihydro-5/-/-cyclopenta[4,5]thieno[2,3-c/]pyrimidinyl, optionally substituted benzothieno[3,2-d]pyrimidinyl and optionally substituted 5,6-dihydrobenzo[/?]cinn0linyl.

One embodiment of this preferred embodiment is a compound of formula (Ia1), as set forth above, selected from the group consisting of: 1 -(5,6,6a,7,8,9,10,10a-octahydrobenzo[/?]quinazolin-2-yl)-/V3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1 -(5,6-dihydro benzo[rt]quinazolin-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 /-/-1,2,4-triazole-3,5-diamlne; A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(6,7,8l9-tetrahydro-5H- cyclohepta[4,5]thieno[2,3-d]pyrimidin-4-yl)-1/-/-1,2,4-triazole-3,5-diamlne; 1-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-c/|pyrimidin-4-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6,7-dihydro-5/-/-cyclopenta[4,5]thieno[2,3-cflpyrimidin-4-yl )-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; A/3-(3-chloro-4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1-(5,6,7,8- tetrahydrobenzo[4,5]thieno[2,3-c/|pyrimidin-4-yl)-1^/-1,2,4-triazole-3,5-diamine; A/3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(5,6,7,8- tetrahydrobenzo[4,5]thieno[2,3-c/lpyrimidin-4-yl)-1/-M, 2,4-triazole-3,5-diamine; 1-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-(^yrimidin-4-yl)-W3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1 -(benzothieno[3,2-c(|pyrimidin-4-yl)-/\/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(7-fert-butyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-c(|pyrimidin-4-yl)-r73-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; and 1 -(5,6-dihydrobenzo[/7]cinnolin-3-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (la), as set forth above, is a compound of formula (la) which is a compound of formula (Ia2):

(Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; RZols selected from the group consisting of-C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R8)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-O-R10-N(R8)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(O)-R8, -R9-N(Rs)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(Re)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted N-heterocydyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoaikyialkyl, optionally substituted cydoalkylalkenyl, optionally substituted cydoalkylaikynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; each R10 is an optionally substituted straight or branched alkylene chain; and each R11 is hydrogen, alkyl, cyano, nitroor-OR8.

One embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of-C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0Rb, -R9-N(R6)C(0)Rb, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0)tN(Re)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R20 is selected from the group consisting of-C(0)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R®-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R®-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis an optionally substituted non-bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-OC(0)-R8, -R9-N(R®)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R0-S(O)tOR8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R^-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2e Is an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)Re, -R9-C(0)0Re, -R9-C(0)N(R6)R7, -R9-N(Re)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(Re)S(0),R8 (where t is 1 or 2), -R9-S(0),0Re (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R8b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois optionally substituted bicyclo[2.2.l]heptanyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and ~R9-S(0)tN(R8)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2i -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyi, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is optionally substituted pyridinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia2) selected from the group consisting of: /\^-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(pyridin-2-yl)-1W-1,2,4-triazole-3,5-diamine; 1 -(6-phenylpyridazin-3-yl)-/V3-(3-fluoro-4-( 4-((1 S,2S,4R)-bicydo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine; and 1 -(4-phenyipyridin-2-yi)-/V3-(3-fiuoro-4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R8b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of-C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(Re)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R®)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyI, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R1°-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R8b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of -C(0)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocydyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted quinazolinyl, optionally substituted isoquinolinyl and optionally substituted naphthyridinonyl.

One embodiment of this preferred embodiment is a compound of formula (Ia2), as set forth above, selected from the group consisting of: 1-(isoquinolin-1-yl)-/V3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-1, 2,4-triazole-3,5-diamine; 1 -(6-chloroquinazolin-4-yl)-/\A3-(4-(4-methylpiperazin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(4-(4-(5-amino-1-(isoquinolin-1-yl)-1H-1,2,4-triazol-3-ylamino)phenyl)plperazin-1- yl)ethanone; /\/3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(isoquinolin-1-yl)-1W-1,2l4-triazole-3,5- diamine; 1-(6,7-dimethoxyquinazolin-4-yl)-/V3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1H-1,2,4- triazole-3,5-diamine; 1 -(4-(4-( 5-amino-1 -(6,7-dimethoxyquinazolin-4-yl)-1 H-1,2,4-triazol-3-ylamino)phenyl)piperazin-1-yl)ethanone; 5-(5-amino-3-(3-f1uoro-4-(4-methylpiperazin-1-yl)phenylamino)-1H-1,2,4-triazol-1-yl)-1,6- naphthyridin-2(1H)-one; 4-(5-amino-3-(3-fluoro-4-(4-methylpiperazin-1-y|)phenylamino)-1H-1,2,4-triazol-1- yl)quinazoline-6,7-diol; 4- (5-amino-3-(3-fluoro-4-(4-methylpiperazin-1 -yl)phenylamino)-1H-1,2,4-triazoM -yl)-6- methoxyquinazolin-7-ol; /V3-(4-chloro-3-(4-ethylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(4-(5-( 5-amino-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazol-3-ylamino)-2-chlorophenyl)piperazin-1-yl)ethanone; 5- (5-amino-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazol-3-ylamino)-2-(4- methylpiperazin-1-yl)benzamide; and 1-(6,7-dimethoxyquinazolin-2-yl)-/\/3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-1l2l4-triazole- 3,5-diamine.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R8b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is an optionally substituted non-bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(Re)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclyfalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted quinazolinyl and optionally substituted isoquinolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia2), as set forth above, selected from the group consisting of: /V5-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1/-/-1,2,4-triazole-3,5-diamine; A/3-(4-(4-(bicyclo[3.2.0]heptan-6-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1 /-/-1,2,4-triazole-3,5-diamine; A/3-(4-(4-cyclohexylpiperazin-1 -yl)phenyl)-1 -(isoquinolin-1 -yl)-1 H-1,2,4-triazoler3,5-diamine; 4-(5-amino-3-(4-(4-cyclohexylpiperazin-1-yl)phenylamino)-1H-1,2,4-triazol-1-yl)-6- methoxyquinazolin-7-ol; A/3-(4-(4-cyclohexylpiperazin-1-yl)-3-fluorophenyl)-1-(isoquinolin-1-yl)-1H-1,2,4-triazole- 3.5- diamine; /V3-(3-chloro-4-(4-cyclohaxylpiperazin-1-yl)phanyl)-1 -(isoquinolin-1 -yl)-1W-1,2,4-triazole- 3.5- diamlne; 4-(5-amino-3-(4-(4-cycloheptylplperazin-1-yl)phenylamino)-1/-/-1,2,4-triazol-1-yl)-6-methoxyquinazolin-7-ol; A/3-(4-(4-cycloheptylpiperazin-1-yl)phenyl)-1-(6l7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazole-3,5-diamine; /V3-(4-(4-cyclooctylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolln-4-yl)-lH-1,2,4-triazole-3,5-diamine; /\/3-(3-chloro-4-(4-cyclohexylpiperazin-1 -yl)phenyl)-1 -(6,7-dimethoxyquinazolin-4-yl)-1 H- 1.2.4- triazole-3,5-diamine; /V3-(4-(4-cyclohexylpiperazln-1-yl)-3-fluorophenyl)-1-(6,7-dimethoxyquinazolin-4-yl )-1/-/- 1.2.4- triazole-3,5-diamine; W3-(4-(4-cycloheptylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyisoquinolin-1-yl)-1/7-1,2,4-triazole-3,5-diamine; and 1-(6,7-dimethoxyquinazolin-2-yl)-/V3-(3-fiuoro-4-(4-cyclohexylpiperazin-1-yl)phenyl )-1 H- 1.2.4- triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZb is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; RZcis an optionally substituted bridged cycloalkyl; RZk is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R®)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloaIkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R®)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R8b, R7b and R86 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of optionally substituted bicyclo[2.2.1]heptanyl, optionally substituted bicyclo[3.2.0]heptan-6-yl, optionally substituted bicyclo[3.3.1]nonanyl and optionally substituted adamantanyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0Re, -R9-N(R6)C(0)R6, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0Re (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R^-CfOMR8)* or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted quinazolinyl, optionally substituted quinoxalinyl, optionally substituted benzo[cf|thiazolyl, optionally substituted isoqulnolinyl, optionally substituted thieno[3,2-cf|pyridazinyl, optionally substituted furo[3,2-c]pyridinyl, optionally substituted thieno[2,3-c(]pyrimidinyl and optionally substituted thieno[3,2-d]pyrimidinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia2), as set forth above, selected from the group consisting of: 1-(benzo[d]thiazol-2-yl)-/\/s-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1 ,2,4-triazole-3,5-diamine; /\/s-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1 H-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(isoquinolin-1-yl )-17/-1,2,4-triazole-3,5-diamine; 1-(benzo[c/]thiazol-2-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-17/-1 ,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(quinoxalin-2-yl)-1/7-1,2,4- triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1/7-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-chloro-7-methylthieno[3,2-c(Ipyrimidin-4-yl)-1/7-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1-yl)phenyl )-1-(2-ch loro-6,7-dimethoxyquinazolin-4-yl )-1 /7-1,2,4-triazole-3,5-diamine; 4-(5-amino-3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenylamino)-1/7-1,2,4-triazol-1-yl)-2-chloro-6-methoxyquinazolin-7-ol; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6-chloroquinazolin-4-yl)-1/7- 1.2.4- triazole-3,5-diamine; 4-(5-amino-3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)-3-fluorophenylamino)-1/7- 1.2.4- triazol-1-yl)-6-methoxyquinazolin-7-ol; A/3-(4-(4-adamantan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxy-quinazolin-4-yl)-1/7- 1.2.4- triazole-3,5-diamine; /V3-(4-(4-(bicyclo[3.3.1]nonan-9-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1 /7-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)-3-fluorophenyl)-1-(6,7-dimethoxyquinazolin-4-yl )-1 /7-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1-(6,7-dimethoxyisoquinolin-1-yl )-1/7-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(thieno[2p3-c/]pyrimidin-4-yl)-1 /7-1,2,4-triazole-3,5-diamine; A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(thieno[3,2-c/]pyrimidin-4-yl)-1 /7-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6-phenylthieno[3,2- c/]pyrimidin-4-yl)-1 Η-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-2-(6-phenylthieno[2,3-c/]pyrimidin-4-yl)-2A/-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1 -(furo[3,2-c]pyridin-4-yl)-1 /-/- 1.2.4- triazole-3,5-diamine; A/3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1 -(6-fluoroquinazolin-4-yl)-1 /-/- 1.2.4- triazole-3,5-diamine; /^-(4-( 1-(bicyclo[2.2.1 ]heptan-2-yl)piperidin-4-yl)phenyl)-1-(2-chloro-7-methylthieno[3,2-c/]pyrimidin-4-yl)-1 /-/-1,2,4-triazole-3,5-diamine; /\Z3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1-yl)phenyl )-1-(2-methylquinazolin-4-yl)-1/-/- 1.2.4- triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-(trifluoromethyl)quinazolin-4-yl)-1A/-1,2,4-triazole-3,5-diamine; /^-(4-( 4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2,5,6-trimethylthieno[2,3-d]pyrimidin-4-yi)-1 /-/-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclot2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(5,6-dimethylthienot2l3-c/]pyrimidin-4-yl )-1/-/-1,2,4-triazole-3,5-diamine; A/3-(4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-chloro-7-methylthieno[3,2-c/]pyrimidin-4-yl)-1/-/-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)-3-fluorophenyl)-1-(2-chloro-7-methyithieno[3,2-c/]pyrimidin-4-yl)-1/-/-1,2,4-triazole-3,5-diamine; A/3-(4-(4-((1R,2R,4S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-chloro-7-methylthieno[3,2-o/]pyrimidin-4-yl)-1 /-/-1,2,4-triazole-3,5-diamine; 1-(2-chlorothieno[3,2-c/]pyrimidin-4-yl)-/V3-(4-(4-((1S,2S,4R)-bicyclot2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl )-1 /-/-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyquinazolin-2-yl)-/V3-(4-(4-((1S,2S,4R)-bicyclot2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine; 1-(5-(thiophen-2-yl)thieno[2,3-d]pyrimidin-4-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl )-1 /-/-1,2,4-triazole-3,5-diamine; 1-(6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(6-(1,1-dimethylethyl)thienot3,2-d]pyrimidin-4-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthienot3,2-c/]pyrimidin-4-yl)-/V3-(4-(4-((1S,2S,4R)-bicyclot2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(thieno[3,2-c/Ipyrimidin-4-yl)-/\A3-(4-(4-((1 S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)-piperazin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1 -(thieno[2,3-c/Jpyrimidin-4-yl)-/\A3-(4-(4-((1 S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)-piperazin- 1- yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(5-methylthieno[2,3-c(lpyrimidin-4-yl)-A/3-(4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-chlorothieno[3,2-cflpyrimidin-4-yl)-/V3-(4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3I2-cdpyrimidin-4-yl)-/V3-(3-fluoro-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine; 1-(thieno[3,2-cOpyrimidin-4-yl)-/\/3-(3-fluoro-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(thieno[2I3-cdpyrimidin-4-yl)-/V3-(3-fluoro-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(6-fluoroquinazolin-4-yl)-W3-(3-fluoro-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(4-methylthieno[3,2-c(lpyridazin-7-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c(lpyrimidin-4-yl)-/V3-(3-methyl-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-chlorothieno[3,2-cdpyrimidin-4-yl)-W3-(2-methyl-4-(4-(bicyclo[2.2.1]heptan- 2- yl)-piperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c(lpyrimidin-4-yl)-A/3-(3-fluoro-4-(4-((1Sl2S,4R)- bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-cdpyrimidin-4-yl)-/V3-(2-methyl-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(4-methylthieno[3,2-c(lpyridazin-7-yl)-A/3-(3-fluoro-4-(4-(bicyclo[2.2,1]heptan-2-yi)-piperazin-1 -yl)phenyl)-1 /-/-1 ^^-triazole-S.S-diamine; 1-(4-methylthieno[3,2-c(lpyridazin-7-yl)-/\/3-(3-methyl-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/-/-1l2l4-triazole-3l5-diamine; 1-(7-methyl-2-chlorothieno[3,2-c(lpyrimidin-4-yl)-A/3-(3-methyl-4-(4-(bicyclo[2.2,1]heptan- 2-yl)piperazin-1-yl)phenyl )-1/-/-1,2,4-triazole-3,5-diamine; 1-(4-methylthieno[3,2-d]pyridazin-7-yl)-A/3-(3-fluoro-4-(4-((1Sl2S,4/?)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 H-1,2,4-triazole-3,5-diamine; 1-(2-chloro-6-methoxy-quinoxalin-3-yl)-/V3-(3-fluoro-4-(4-(( 1 S,2S,4/?)- bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxy-1-methylphthalazin-4-yl)-/V3-(3-fluoro-4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(4-methylthieno[3,2-d]pyridazin-7-yl)-/V3-(3-chloro-4-(4-((2S)-bicyclo[2.2.1]heptan-2- yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(4-methylthieno[3,2-d]pyridazin-7-yl)-/V3-(3-methyl-4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-m-tolylthieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-(3-cyanophenyl)thieno[3,2-d]pyrimidin-4-yl)-A/3-(4-(4-(bicyclo[2.2.1]heptan- 2-yl)piperazin-1 -yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-(2-chlorophenyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-((2S)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-benzo[d][1,3]dioxole -5-ylthieno[3,2-c(]pyrimidin-4-yl)-/V3-(4-(4-((2S)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-pyridin-4-ylthieno[3,2-c(]pyrimidin-4-yl)-/V3-(4-(4-((2S)-bicyclo[2.2.1]heptan- 2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-(3-(methylsulfonyl)aminophenyl)thieno[3,2-c/]pyrimidin-4-yl)-/V3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-(3-(pyrrolidin-1-yl)prop-1-enyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-((2S)-bicyclot2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-(3-(4-methylpiperazin-1-yl)prop-1-enyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-((2S)-bicyclo[2.2.1 ]heptan-2-yl)piperazin-1-yl)phenyl )-1/-/-1,2,4-triazole-3,5-diamine; 1-(7-methy|-2-(3-(morpholin-4-yl)prop-1-enyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c/|pyrimidin-4-yl)-A/3-(3-chloro-4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-thieno[3,2-c/]pyrimidin-4-yl-/\/3-(3-chloro-4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-thieno[2,3-d]pyrimidin-4-yl-/V3-(3-chloro-4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2- yOpiperazin-l-yOphenyO-IH-l^^triazole-S.S-diamine; 1-(7-methylthieno[3,2-c/| pyrimidin-4-yl)-A/3-(3-fluoro-4-(4-((1Sl2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1/-/-1,2,4-triazole-3,5-diamine 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-/V3-(3-fluoro-4-(3-(R)-methyl-4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-0^10^^-4-^)-/^-( 3-fluoro-4-(3-(S)-methyl-4- (bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3, 5-diamine; 1-(7-methylthieno[3l2-rf|pyrimidin-4-yl)-/V3-(3-fluoro-4-(3-(/?)-methyl-4-((1S)2Sl4/?)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-/\/3-(3-fluoro-4-(3-(S)-methyl-4-((1S,2Sl4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthteno[3,2-0|pyrimidin-4-yl)-/V3-(3-methyl-4-(4-((1S,2S,4R)- bicyclop^.lIheptan^-yOpiperazin-l-yOphenyO-IW-l^^-triazole-S,5-diamine; 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-A/3-(3-methyl-4-(3-(S)-methyl-4-((1S,2Sl4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1R-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-A/3-(3-methyl-4-(3-(R)-methyl-4-((1Sl2Sl4R)-bicyclb[2.2.1]heptan-2-yl)piperazin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1 -thieno[3,2-c/|pyrimidin-4-yl-/V3-(3-fluoro-4-(3-(S)-methyl-4-(( 1 S.2SAR)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 R-1,2,4-triazole-3,5-diamine; and 1-(2-chloro-7-methylthieno[3,2-c/|pyrimidin-4-yl)-W3-(3-methyl-4-(3-(S)-methyl-4- ((1 S,2S,4R)-bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1 H-1,2,4-triazole- 3,5-diamine.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR®b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(Reb)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of -C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R8-C(0)N(R6)R7, -R9-N(R8)C(0)0R8, -R9-N(Rb)C(0)R8, -R9-N(R®)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R8-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted N-heterocyclyl; each R® is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R^-OR8®, -R9b-C(0)0R8b, -R9b-N(R®b)R7b and -R9b-C(0)N(R6b)R7b, where each R®b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of-C(0)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R®-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted h eterocycl y la I ky I, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted 5,6-dihydrobenzo[/i]quinazolinyl and optionally substituted 5,6-dihydrobenzo[h]cinnolin-3-yl.

One embodiment of this preferred embodiment is a compound of formula (Ia2), as set forth above, selected from the group consisting of: 1-(5,e'dihydrobenzot/ilquinazolin^-yO-A^-i^i^methylpiperazin-l-yOphenyl )-1 H-1,2,4-triazole-3,5-diamine; and 1-(5,6-dihydrobenzo[ft]cinnolin-3-yl)-/V3-(4-(4-methylpiperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl;

Rzb is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R6b, -R9b-N(R8b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois an optionally substituted non-bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R6, -R9-C(0)0Re, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R6)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted 5,6-dihydrobenzo[/j]quinazolinyl, optionally substituted 5,6-dihydrobenzo[ft]cinnolinyl and optionally substituted phenanthridinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia2), as set forth above, selected from the group consisting of: /\/3-(4-(4-cyclohexylpiperazin-1 -yl)phenyl)-1 -(5,6-dihydrobenzo[/j]quinazolin-2-yl)-1 H- 1,2,4-triazole-3,5-diamlne; A/3-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1 -(5,6-dihydrobenzo[ft]cinnolin-3-y] )-1 W-1,2,4-triazole-3,5-diamine; and 1 -(phenanthridin-e-ylHV^S-fluoro^-^-cyclopentylpiperazin-l-yOphenylJ-l H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein: R1, R4 and R5 are each Independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(Reb)R7b and -R9b-C(0)N(R8b)R7b, where each R6b, Rn and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)Rb. -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioalkyi, optionally substituted cycioalkylalkyl, optionally optionally substituted heterocyclyi, optionally substituted heterocyclyialkyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioalkylalkyl, optionally substituted heterocyclyi, optionally substituted heterocyclyialkyi, optionally substituted heteroaryi, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia2), as set forth above, is a compound of formula (Ia2) wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b Is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois optionally substituted bicyclo[2.2.1]heptanyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyi, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0),R8 (where t Is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)ORe and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted 6,7-dihydro-5H-cydopenta[4,5]thieno[2,3-ofjpyrimidinyl and optionally substituted pyrido[2,3-b]pyrimido[4,5-d]thiopheneyl.

One embodiment of this preferred embodiment is a compound of formula (Ia2), as set forth above, selected from the group consisting of: /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dihydro-5H- cyclopenta[4,5]thieno[2,3-of]pyrimidin-4-yl)-1Ay-1,2,·4-triazole-3,5-diamine; and 1-(pyrido[2,3-b]pyrimido[4,5-d]thiophene-4-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazln-1-yl)phenyi)-1/-/-1,2,4-triazole-3,5-dlamine.

Another embodiment of the compounds of formula (la), as set forth above, Is a compound of formula (la) which is a compound of formula (Ia3):

(Ia3) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(Re)R7; R2® is selected from the group consisting of halo, -OR8, -C(0)R8, -C(0)OR8, -R10e-N(R6)R7, -R10e-C(O)N(R®)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10e Is an optionally substituted straight or branched alkylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -r9-o-r10-cn, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R6)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-O-R10-N(R8)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R8)S(0)tR8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(Re)R7 (where t is 1 or 2); each R6 and R7 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloaIkylaIkenyI, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R1°-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond or an optionally substituted straight or branched alkylene chain; each R10 is an optionally substituted straight or branched alkylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or-OR®.

One embodiment of the compounds of formula (Ia3), as set forth above, is a compound of formula (Ia3) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2e is selected from the group consisting of halo, -OR®, -C(0)R®, -C(0)0R®, -R10e-N(R6)R7, -R10e-C(O)N(R6)R7, optionally substituted heterocydyl and optionally substituted heteroaryl, where each R10e is an optionally substituted straight or branched alkylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR®; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocydyl, optionally substituted heterocyclylalkenyl, -R9-OR®, -R9-0C(0)-R®, -R9-N(R6)R7, -R9-C(0)R®, -R9-C(0)0R®, -R9-C(0)N(R®)R7, -R9-N(R6)C(0)0R®, -R9-N(R6)C(0)R®, -R9-N(R6)S(0)tR® (where t is 1 or 2), -R9-S(0),0R® (where t is 1 or 2), -R9-S(0)pR® (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cydoalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R1o-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R8 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted phenyl and optionally substituted pyridinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia3), as set forth above, selected from the group consisting of: 1-(4-isopropylphenyl)-/V3-(4-morpholinophenyl)-1H-1,2,4-triazole-3,5-diamine; /V^-methoxyphenyO-l -(pyridin-2-yl )-1 H-1,2,4-triazole-3,5-diamine; ethyl 4-(5-amino-1-(2-chloropyridin-4-yl)-1H-1,2,4-triazol-3-ylamino)benzoate; (S^-ethyl 4-(5-amino-1-(2-(2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)pyridin-4-yl )-1/-/-1,2,4-triazol-3-ylamino)benzoate; {3)-4-( 5-amino-1-(2-(2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)pyridin-4-yl)-1H-1,2,4-triazol- 3-ylamino)benzoic acid; 1-(4-( 5-amino-1-(2-fluorophenyl)-1/+1,2,4-triazol-3-ylamino)phenyl)ethanone; 1-(pyridin-2-yl )-ΛΛ*-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(pyridin-2-yl)-/V3-(3,4,5-trifluorophenyl)-1 A/-1,2,4-triazole-3r5-diamine; 3-(5-amino-1-(pyrid(n-2-yl)-1H-1,2,4-triazol-3-ylamino)phenol; 1-phenyl-N3-(4-(methylaminocarbonyl)phenyl)-N5-methyl-1H-1,2,4-triazole-3,5-diamine; 1-phenyl-N3-(4-(ethyloxocarbonyl)phenyl)-N5-methyl-1H-1,2,4-triazole-3,5-diamine; 1 -(6-phenylpyridazin-3-yl)-/V3-(3-fluoro-4-(4-(pyrrolidin-1 -yl)piperidin-1 -yl)phenyl)-1 H- 1,2,4-triazole-3,5-diamine; and 1-(4-phenylpyridin-2-yl)-/V3-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia3), as set forth above, is a compound of formula (Ia3) wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZe Is selected from the group consisting of halo, -OR®, -C(0)R®, -C(0)0R®, -R10e-N(R6)R7, -R10e-C(O)N(R®)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10e is an optionally substituted straight or branched alkylene chain; R2d and Ra are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR®; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR®, -R9-0C(0)-R®, -R9-N(Re)R7, -R9-C(0)R®, -R9-C(0)0R®, -R9-C(0)N(R®)R7, -R9-N(R6)C(0)0R®, -R9-N(R6)C(0)R®, -R9-N(R®)S(0),R® (where t is 1 or 2), -R9-S(0)t0R® (where t is 1 or 2), -R9-S(0)pR® (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyI, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR®, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR® and -R10-C(O)N(R®)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R® is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted quinoxalinyl, optionally substituted quinazolinyl, optionally substituted thieno[3,2-of|pyrimidinyl and optionally substituted isoquinolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia3), as set forth above, selected from the group consisting of: 1-(4-(5-amino-1-(quinoxalin-2-yl)-1H-1,2,4-triazol-3-ylamino)phenyl)ethanone; 3- (4-(5-amino-1-(quinoxalin-2-yl)-1H-1,2,4-triazol-3-ylamlno)phenyl)-1-(pyrrolidin-1- yl)propan-1-one; 1-(6,7-dimethoxyquinazolin-4-yl)-/V3-(4-(1-methylpiperidin-3-yloxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(isoquinolin-1-yl)-A/3-(4-(1-methylpiperidin-3-yloxy)phenyl)-1H-1,2,4-triazole-3,5- diamine; 1-(isoquinolin-1-yl)-/V3-(4-morpholinophenyl)-1H-1,2,4-trlazole-3,5-diamine; 1-(6,7-dimethoxyqulnazolin-4-yl)-/V3-(4-morpholinophenyl)-1H-1,2,4-triazole-3,5-diamine; /V3-(3-chloro-4-morphollnophenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazole-3,5-diamine; /^-(S-chloro^-morphollnophenyO-l -(6-chloroquinazolin-4-yl)-1 H-1,2,4-triazole-3,5-diamine; /\/3-(3-fluoro-4-morpholinophenyl)-1 -(isoquinolin-1 -yl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyquinazolin-4-yl)-W3-(3-fluoro-4-morpholinophenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(isoquinolin-1-yl)-A/3-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-1,2,4-triazole-3,5- diamine; /V3-(4-((R)-3-(dimethylamino)pyrrolidin-1-yl)phenyl)-1-(isoquinolin-1-yl)-1H-1,2,4-triazole- 3.5- diamine; A/3-(4-((S)-3-(dimethylamino)pyrrolidin-1 -yl)phenyl)-1 -(isoquinolin-1 -yl)-1 H-1,2,4-triazole- 3.5- diamine; 1-(isoquinolin-1-yl)-W3-(4-(oxazol-5-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(isoquinolin-1-yl)-W3-(4-(1-methylpiperidin-4-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1 -(6,7-dimethoxyquinazolin-4-yl)-/V3-(4-(1-methylpiperidin-4-yl)phenyl)-1 H-1,2,4-triazole- 3.5- diamine; 4- (5-amino-3-(4-(1-methylpiperidin-4-yl)phenylamino)-1H-1,2,4-triazol-1-yl)-6- methoxyquinazolin-7-ol; 1-(6,7-dimethoxyquinazolin-4-yl)-/V3-(4-((S)-3-(dimethylamino)pyrrolidin-1-yl)phenyl )-lH- 1,2,4-triazole-3,5-diamine; 4-(5-amino-3-(4-(1-methylpiperidin-4-yl)phenylamino)-1H-1,2,4-triazol-1-yl)quinazoline- 6,7-diol; 1 -(ej-dimethoxyquinazolin^-yO-A/^-^-methylpiperazin-l -yl)methyl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyisoquinolin-1-yl)-A/3-(4-(1-methylpiperidin-4-yl)phenyl)-1W-1,2,4-triazole- 3.5- diamine; 1-(6,7-dimethoxyquinazolin-4-yl)-/V3-(4-(4-(cyclopentyl)piperazin-1-ylcarbonyl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-A/3-(4-(4-(cyclopentyl)piperazin-1-ylcarbonyl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-chlorothieno[3,2-of]pyrimidin-4-yl)-A/3-(4-((2-(pyrrolidin-1-yl)ethyl)aminocarbonyl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyquinazolin-4-yl)-A/3-(3-fluoro-4-(4-piperidin-1-ylpiperidin-1-yl)phenyl)-1H- 1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-chlorothieno[3,2-c/]pyrimidin-4-yl)-A/3-(3-fluoro-4-(4-piperidin-1-ylpiperidin-1 -yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-chlorothieno[3,2-c/]pyrimidin-4-yl)-A/3-(3-fluoro-4-(3-diethylaminopyrrolidin- 1- yl)phenyl )-1 W-1,2,4-triazole-3,5-diamine; 1-(7-methyl-2-chlorothieno[3,2-c(]pyrimidin-4-yl)-A/3-(3-fluoro-4-(isoindolin-2-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1 -(6,7-dimethoxyquinazolin-4-yl)-A/3-(3-fluoro-4-(isoindolin-2-yl)phenyl )-1 H-1,2,4-triazole- 3.5- diamine; 1-(2-chloro-6-methoxy-quinoxalin-3-yl)-A/3-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1- yl)phenyl)-1H-1,2,4-triazole-3,5-dlamine; 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-/V3-(3-fluoro-4-(4-(2-azabicyclo[2.2.1]heptan-2-yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-A/3-(4-(1-(bicyclo[2.2.1]heptan-2-yl)piperidin-4-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; and 1-(7-methylthieno[3,2-c(]pyrimidin-4-yl)-A/3-(3-fluoro4-(1-((1SI2S,4/?)-bicyclo[2.2.1]heptan- 2- yl)piperidin-4-yi )phenyl )-1 H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia3), as set forth above, is a compound of formula (Ia3) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2® is selected from the group consisting of halo, -OR8, -C(0)R8, -C(0)0R8, -R10®-N(R6)R7, -R10e-C(O)N(Re)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10® is an optionally substituted straight or branched alkylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of a tricyclic aryl or a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(Re)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R®)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted 5,6-dihydrobenzo[h]cinnolinyl, optionally substituted 5/7-chromeno[4,3-c]pyridazinyl and optionally substituted phenanthridinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia3), as set forth above, selected from the group consisting of: 1-(5,6-dihydrobenzo[/7]cinnolin-3-yl)-/V3-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine; 1-(8-methoxy-5,5-dimethyl-5W-chromeno[4,3-c]pyridazin-3-yl)-/V3-(3-fluoro-4-(4(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine; 1-(phananthridin-6-yl)-A/3-(4-(1-methylpiparidln-4-yl)phanyl)-1W-1,2,4-triazole-3I5-diamine; and 1-(phenanthridin-6-yl)-A/3-(3-methyl-4-(4-pyriOlidin-1-ylpiperidin-1-yl)phenyl)-1H-1,2,4-tri azole-3,5-diamine.

Another embodiment of the compounds of formula (la), as set forth above, is a compound of formula (la) which is a compound of formula (Ia4): (Ia4) wherein:

R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; R2h is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where R®h is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl;

Rzd is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2', Ra and R2' are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocydylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(Re)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t Is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R^SiOJtNfR^R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted N-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R® is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

One embodiment of the compounds of formula (Ia4), as set forth above, is a compound of formula (Ia4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of hydrogen, -N(R8h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where R6h is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R®-N(R8)R7; R2f, R2' and R2* are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R®-OR8, -R®-0C(0)-Re, -R9-N(R6)R7, -R®-C(0)R8, -R®-C(0)0R8, -R®-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R®-N(Re)C(0)R8, -R9-N(Re)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R®-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia4), as set forth above, is a compound of formula (Ia4) wherein: R1, R4 and R5 are each Independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where R6h is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2f, R2' and R2) are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R^OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R^OJpR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyf, hydroxyalkyf, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocydyl; each R8 is independently seleded from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia4), as set forth above, is a compound of formula (Ia4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of optionally substituted heterocyclyl and optionally substituted heteroaryl; R2d, R2f, R2' and R2J are each independently hydrogen; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocydyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted thieno[3,2-c/|pyrimidinyl and optionally substituted quinazolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia4), as set forth above, selected from the group consisting of: 1-(7-methyl-2-chlorothieno[3,2-c/|pyrimidin-4-yl)-A/3-(7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5/-/-benzo[7]annulene-2-yl)-1 H-1,2,4-triazole-3,5-diamine; and 1-(6,7-dimethoxyquinazolin-4-yl)-W3-(7-pyrrolidin-1-yl-6,7,8,9-tetrahyd ro-5/+ benzo[7]annulene-2-yl)-1 H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia4), as set forth above, is a compound of formula (Ia4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2” is -N(R6h)R7h where R6h is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2', R21 and R2i are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R®)C(0)0R®, -R9-N(R®)C(0)R®, -R9-N(R®)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR® (where p is 0,1 or 2), and -R9-S(0),N(R®)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R®)2, -R10-C(O)OR® and -R10-C(O)N(R®)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R® is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ia4), as set forth above, is a compound of formula (Ia4) wherein: R1, R4 and R® are each independently selected from the group'consisting of hydrogen and alkyl; R2h is -N(R®h)R7h where R®h is hydrogen or alkyl and R7h is optionally substituted bicyclo[2.2.1 ]heptanyl; R2d is independently selected from the group consisting of hydrogen, halo and -OR®; R2f, R21 and R2J are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)OR8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R81 -R9-N(R6)C(0)R8, -R9-N(R8)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a dired bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted thieno[3,2-c(]pyrimidinyl and optionally substituted quinazolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ia4), as set forth above, selected from the group consisting of; 1-(7-methyl-2-chlorothieno[3,2-c(]pyrimldin-4-yl)-/\/3-(7-(/V-methyl-/V-bicyclo[2.2.1]heptan- 2-yl)amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5- diamine; 1-(7-methyl-2-chlorothieno[3,2-d]pyrimidin-4-yl)-W3-(7-(/V-bicyclo[2.2.1]heptan-2- yl )amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl )-1/-/-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyquinazolin-4-yl)-W3-(7-(/V-bicyclo[2.2.1]heptan-2-yl)amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1W-1,2,4-triazole-3,5-diamine; and 1-(6,7-dimethoxyquinazolin-4-yl)-W3-(7-(/V-methyl-/V-bicyclo[2.2.1]heptan-2-yl)amino- 6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1/-/-1,2,4-triazole-3,5-diamlne. Another embodiment of the compounds of formula (Ia4), as set forth above, is a compound of formula (Ia4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is hydrogen; R2d is -R9-N(R6)R7; R* R2i and R2i are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 Is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain,

One embodiment of this preferred embodiment is the compound of formula (Ia4), as set forth above, which is 1-(7-methyl-2-chlorothieno[3l2-£/|pyrimidin-4-yl)-/V3-(8-(2- diethylaminoethyl)-9-hydroxy-6,7,8,9-tetrahydro-5W-benzo[7]annulene-2-yl)-1f/-1,2,4- triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ia4), as set forth above, is a compound of formula (Ia4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where Reh is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2', R2' and RZ| are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R®-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR6, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted TV-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (I), as set forth above in the Summary of the Invention, is wherein the compound of formula (I) is a compound of formula (lb):

wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; R2 is aryl optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloaikyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R8)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-O-R10-N(R6)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R9-N(Rb)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(Re)R7 (where t is 1 or 2); R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R6)R7, -R9-O-R10-S(O)pR8 (where p is 0, 1 or 2), -R9-O-R10-N(R6)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R8)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(Re)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyelyl; each R® is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycioalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or-OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.

One embodiment of the compounds of formula (lb), as set forth above, is a compound of formula (lb) which is a compound of formula (Ib1): (Ib1) wherein:

R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(Re)R7; R28 is -R^-NfR^R73 where R63 and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted A/-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; RZg is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R"-C(0)R89, -R"-C(0)0R8g, -R"-N(R69)R79 and -R"-C(0)N(R89)R79, where each R®8, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R®9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkyfalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(Re)R7, -R9-O-R10-S(O)pR8 (where p is 0.1 or 2), -R9-O-R10-N(R6)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or -OR®.

One embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R2s Is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R9g-C(0)R®e, -R"-C(0)0R89, -R"-N(R®9)R79 and -R"-C(0)N(R69)R79, where each R69, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R®, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R®, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R8)C(0)R®, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR®, -R10-CN, -R10-NO2, -R10-N(R®)2, -R10-C(O)OR® and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted Af-heterocyclyl; each R8 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2ais -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted A/-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R2g is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR8b, -R"-C(0)R89, -R"-C(0)0R89, -R"-N(R®9)R79 and -R"-C(0)N(R89)R79, where each R89, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R" is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a monocyclic aryl optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0)|R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R2a is optionally substituted 2-(piperidinyl)ethyl and R3 is optionally substituted phenyl.

One embodiment of this preferred embodiment is a compound of formula (Ib1), as set forth above, which Is 1-phenyl-/V5-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-dlamine.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted Af-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR88, -R99-C(0)R88, -R98-C(0)0R88, -R99-N(R69)R79 and -R^CiOMR^R79, where each R89, R7® and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9g is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a monocyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R^OCiOJ-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0Rb, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each Re and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and Rs are each independently selected from the group consisting of hydrogen and alkyl; RZais -R10a-N(R8a)R7a where R8a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted W-heterocyclyi, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R9fl-C(O)R80, -R99-C(0)0R89, -R"-N(R69)R79 and -R99-C(0)N(R69)R79, where each R6g, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a bicyclic aryi and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R8)C(0)0R8, -R9-N(Re)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR· and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocydyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2ais -R10a-N(R8a)R7a where R8a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R99-C(0)R89, -R"-C(0)0R89, -R99-N(R69)R7b and -R99-C(0)N(R69)R79, where each R89, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a bicyclic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocydyl, optionally substituted heterocyclylalkenyl, -R9-OR®, -R9-0C(0)-R®, -R9-N(R6)R7, -R9-C(0)R®, -R9-C(0)0R®, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R®, -R9-N(R6)C(0)R®, -R9-N(R®)S(0),R® (where t is 1 or 2), -R9-S(0),0R® (where t is 1 or 2), -R9-S(0)pR® (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR®, -R10-CN, -R10-NO2, -R10-N(R®)2, -R10-C(O)OR® and -R10-C(O)N(R®)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocyclyl; each R® is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R®a)R7a where RSa and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl, and R10a Is an optionally substituted straight or branched alkylene chain; R20 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R"-C(0)R®9, -R"-C(0)0R®9, -R"-N(R®9)R79 and -R^CiOMR^R79, where each R®9, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R®9 is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a bicyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-ORB, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0R8, -R9-N(R6)C(0)R8, -R8-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2l or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where R8a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R^CtOJR89, -R"-C(0)0R89, -R"-N(R89)R79 and -R"-C(0)N(R89)R79, where each R89, R79 and R®9 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cydoalkyl, optionally substituted cycioalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R^-OR89, -R^CiOJR89, -R"-C(0)0R89, -R^-NiR^JR79 and -R"-C(0)N(R69)R79, where each R69, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a tricyclic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylaIkyI, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib1), as set forth above, is a compound of formula (Ib1) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZa is -R10a-N(R6a)R7a where R8a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted AMieteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R^CXOJR89, -R"-C(0)0R89, -R9g-N(R89)R79 and -R"-C(0)N(R68)R79, where each R®9, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a tricyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-Re, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0Re, -R9-N(R6)C{0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cydoalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (lb), as set forth above, is a compound of formula (lb) which is a compound of formula (Ib2): (Ib2)

wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R® and -C(0)N(R®)R7; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and Reb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois selected from the group consisting of -C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycioaikyi; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, thloxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -r9-o-r10-cn, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R8)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-O-R10-N(R8)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R8)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocydyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; each R10 is an optionally substituted straight or branched alkylene chain; and each R11 is hydrogen, alkyl, cyano, nitroor-OR8.

One embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of-C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(Rb)C(0)0R8, -R9-N(Rb)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b Is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R8b)R7b and -R9b-C(0)N(Reb)R7b, where each R8b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois selected from the group consisting of -C(0)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(Re)C(0)0R8, -R8-N(R®)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R®-S(0),0R· (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(Re)R7 (where t is 1 or 2); each R6 and R7 Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R^-qopR8 and -Ρ10-Ο(Ο)Ν^)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein; R1, R4 and R® are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is an optionally substituted non-bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R6)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; RZcls selected from the group consisting of -C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl;

Rzk is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2i -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R6 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R®b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R8b)R7b, where each Reb, R7b and Reb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is selected from the group consisting of -C(0)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR®, -R9-0C(0)-Re, -R9-N(R6)R7, -R9-C(0)Re, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(Re)C(0)0R8, -R9-N(Re)C(0)R8, -R9-N(R8)S(0)iR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R8)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is optionally substituted quinazolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ib2), as set forth above, which is Hb-chloroquinazolin-^-ylJ-A/^-i^methylpiperazin-l-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis an optionally substituted non-bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(Re)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t Is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2l or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is optionally substituted quinazolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ib2), as set forth above, which is A/s-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl )-1 W-1,2,4-triazole-3,5-dlamine.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocydyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R8)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R0-S(O)tOR8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R8)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted Λ/-heterocyclyI; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R6 are each Independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R8b, R7b and RSb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois optionally substituted bicyclo[2.2.1]heptanyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0)tR8 (where t is 1 or 2), -R9-S(0)i0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted AZ-heterocyelyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted thieno[3,2-c/|pyrimidinyl, optionally substituted benzo[£/]thiazolyl and optionally substituted quinazolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ib2), as set forth above, selected from the group consisting of: 1-(6-(1,1 -di methylethyl)thieno[3,2-d] py ri m i d in-4-yl )-A/®-(4-(4-(bi cyclo[2.2.1 ]heptan-2-yl )-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(benzo[£/]thiazol-2-yl)-/\/5-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H- 1,2,4-triazole-3,5-diamine; and /V5-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl )-1/-/-1,2,4-triazole-3,5-dlamine.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois selected from the group consisting of -C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2K is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocydylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR6 and -R10-C(O)N(R8)2, or any Rfl and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and Rs are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ois selected from the group consisting of -C(0)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocydylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)OR8, -R9-C(0)N(R6)R7, rR9-N(R6)C(0)0R8, -R9-N(Re)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)|0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(Re)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocydyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R6 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R8b)R7b and -R9b-C(0)N(R6b)R7b, where each RBb, R7b and Reb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R20 is an optionally substituted non-bridged cycloalkyl; R2k Is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-ORB, -R9-0C(0)-Rb, -R9-N(Rb)R7, -R9-C(0)Rb, -R^CtOPR8, -R9-C(0)IM(R6)R7, -R9-N(R6)C(0)0Rb, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each Re and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is optionally substituted phenanthridinyl.

One embodiment of this preferred embodiment Is a compound of formula (Ib2), as set forth above, which is 1-(phenanthridin-6-yl)-/\/®-(3-fluoro-4-(4-cyclopentylpiperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ib2), as set forth above, is a compound of formula (Ib2) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)OR8, -R9-C(0)N(R8)R7, -R9-N(R6)C(0)0Rb, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2i -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (lb), as set forth above, Is a compound of formula (lb) which is a compound of formula (Ib3):

(Ib3) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; R2a is selected from the group consisting of halo, -OR8, -C(0)R®, -CfOJOR8, -R10e-N(R6)R7, -R10e-C(O)N(R6)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10e is an optionally substituted straight or branched alkylene chain; R2d and Rzf are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -r9-o-r10-cn, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R8)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-O-R10-N(Re)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-OqO)-R8, -R9-N(Re)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(R6)C(0)0R8, -R9-N(R8)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R® and R7 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond or an optionally substituted straight or branched alkylene chain; each R10 is an optionally substituted straight or branched alkylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or-OR8.

One embodiment of the compounds of formula (Ib3), as set forth above, is a compound of formula (Ib3) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2® is selected from the group consisting of halo, -OR8, -C(0)R8, -C(0)0R8, -R10e-N(R8)R7, -R10e-C(O)N(R8)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10® is an optionally substituted straight or branched alkylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R8)R7, -R9-C(0)R8, -R9-C(0)0Ra, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib3), as set forth above, is a compound of formula (Ib3) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2® is selected from the group consisting of halo, -OR8, -C(0)R8, -C(0)0R8, -R10e-N(R8)R7, -R10®-C(O)N(Re)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10e is an optionally substituted straight or branched alkylene chain; R2d and R21 are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 Is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)tOR8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NOZ, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 Is an optionally substituted straight or branched alkylene chain.

Of this embodiment, a preferred embodiment is wherein R3 is selected from the group consisting of optionally substituted qulnoxalinyl, optionally substituted quinazolinyl and optionally substituted isoquinolinyl.

One embodiment of this preferred embodiment is a compound of formula (Ib3), as set forth above, selected from the group consisting of: A/®-(4-((1 -methylpyrrolidin-2-yl)methoxy)phenyl)-1 -(quinoxalin-2-yl)-1 H-\,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyquinazolin-4-yl)-/V5-(4-(1-methylpiperidin-3-yloxy)phenyl)-1H-1,2,4~ triazole-3,5-diamine; and 1-(isoquinolin-1-yl)-A/5-(4-morpholinophenyl)-1H-1,2,4-triazole-3,5-diamine.

Another embodiment of the compounds of formula (Ib3), as set forth above, is a compound of formula (Ib3) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZe is selected from the group consisting of halo, -OR8, -C(0)R8, -C(0)0R8, -R10e-N(R6)R7, -R10e-C(O)N(R8)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10e is an optionally substituted straight or branched alkylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of a tricyclic aryl ora tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R^OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R^CiOJR8, -R^CfOpR8, -R9-C(0)N(R8)R7, -R9-N(Re)C(0)0Ra, -R9-N(R8)C(0)RB, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0)t0Ra (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (lb), as set forth above, Is a compound of formula (lb) which is a compound of formula (Ib4):

(Ib4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(Re)R7; RZh is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where RBh is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl;

Rzd is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R8)R7;

Ra, R2i and RZ) are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-OR8, -r9-o-r10-cn, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R8)R7, -R9-0-R1 °-S(0)PR8 (where p is 0,1 or 2), -R9-O-R10-N(R6)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R8)R7, -R9-N(Re)C(0)0R8, -R9-N(Rb)C(0)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(Re)R7 (where t is 1 or 2); each R6 and R7 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted cydoalkylalkenyl, optionally substituted cydoalkylalkynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NOZ, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cydoalkylalkyl, optionally substituted cydoalkylalkenyl, optionally substituted cydoalkylalkynyl, optionally substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a dired bond or an optionally substituted straight or branched alkylene chain; each R10 Is an optionally substituted straight or branched alkylene chain; and each R11 is hydrogen, alkyl, cyano, nitre or -OR8.

One embodiment of the compounds of formula (Ib4), as set forth above, is a compound of formula (Ib4) wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where Reh is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2f, R2i and R2) are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(Re)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R8)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R1°-CN, -R10-NO2, -R10-N(R8)z, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib4), as set forth above, is a compound of formula (Ib4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where Reh is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(Re)R7; R2f, R2' and R2) are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is-selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)Rb, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R1q-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted Af-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

Another embodiment of the compounds of formula (Ib4), as set forth above, is a compound of formula (Ib4) wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZh is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where R6h is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl;

Rzd is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; RZf, R2' and RZ) are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R^CiOJOR8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R8)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2),.-R9-S(0)pR8 (where p is 0,1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R1°-CN, -R10-NO2, -R1°-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(Re)z, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

In particular embodiments, in compounds of formula (la) and (lb), R2 is optionally substituted phenyl or optionally substituted 6,7,8,9-tetrahydro-5H-benzo[7]annulenyl and R3 is selected from the group consisting of optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted quinoxalinyl, optionally substituted benzothlophenyl, optionally substituted benzimidazoyl, optionally substituted phthalazinyl, optionally substituted quinazolinyl, optionally substituted quinolinyi, optionally substituted cyclopenta[d]pyrimidinyl, optionally substituted isoquinolinyl, optionally substituted thienopyrimidinyl, optionally substituted 5,6,7,8-tetrahydrobenzo[4,5]thienopyrimidinyl, optionally substituted thienopyridinyl, optionally substituted 6,7-dihydro-5H-cyclopenta[4,5]thienopyrimidinyl, optionally substituted furopyridinyl, optionally substituted benzothienopyrimidinyl, optionally substituted dihydrobenzo[f?]quinazolinyl, optionally substituted octahydrobenzo[/j]quinazolinyl, optionally substituted dihydrobenzo[h]cinnolinyl, optionally substituted tetrahydroqulnazolinyl, optionally substituted naphthyridin-2(1H)-one-yl, optionally substituted pyrido[4,3-c]pyridazinyl, optionally substituted tetrahydro-5H-cyclohepta[4,5]thienopyrimidinyl, optionally substituted 5,6-dihydrobenzo[/j]quinazolinyl, optionally substituted pyridopyrimido[4,5-d]thiophenyl, optionally substituted phenanthridinyl, optionally substituted thienopyridazinyl and optionally substituted chromeno[4,3-c]pyridazinyl; where the optional substitutents on each R2 and R3 group are independently selected from the group consisting of 2-(piperidin-1 -yI)ethoxy, 2-(pyrrolidln-l-yl)ethoxy, alkyl, halo, haloalkyl, sulfonamido, morpholino, alkoxy, alkylamino, dialkylamino, hydroxy, phenyl, carboxybenzyl, benzyloxy, piperazinyl (optionally substituted with alkyl), cycloalkyl, acyl, bicycloalkyl, thiophenyl, benzodioxanyl, aminosulfonylalkyl, (pyrrolidin-1 -yl)prop-1 -enyl, (alkylpiperazin-1 -yl)prop-1-enyl, (morpholin-4-yl)prop-1-enyl, carboxyalkyl, (pyrrolidin-l-ylmethyl)pyrrolidinyl, (pyrrolidin-1 -yl)propan-1 -one-yl, 1 -alkylpiperidin-3-yloxy, (4-alkylpiperazin-1-yl)methyl, 3-(dialkylamino)pyrrolidin-l-yl, 1 -alkylpiperidin-4-yl, 4-(pyrrolidin-1 -yl)piperidin-1 -yi, 4-(cycloalkyl)piperazin-l-ylcarbonyl, (2-(pyrrolidin-1-yl)ethy!)aminocarbonyl, 4-piperidin-1-ylpiperidin-1-yl, 3-alkylaminopyrrolidin-1-yl, (4-alkylpiperazin-1-yl)piperidin-1-yl, 4-isoindolin-2-yl, alkylaminocarbonyl, 4-(2-azabicyclo[2.2.1]heptan-2-yl)piperidin-1-yl, (1-(bicyclo[2.2.1 ]heptan-2-yl)piperidin-4-yl, 4-( 1 -alkylpyrrolidin-2-yl)methoxy, 1- alkylpiperidin-3-yloxy, pyrrolidinyl, N-alkyl-N-bicyclo[2.2.1]heptan-2-ylamino, N-bicyclo[2.2.1]heptan-2-ylamino and 2-alkylaminoethyl.

Of the various aspects of the pharmaceutical compositions of the invention comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of formula (I), as set forth above in the Summary of the Invention, certain embodiments are preferred.

One embodiment of these pharmaceutical compositions is wherein the compound of formula (I) therein is selected from any one embodiment of the compound of formula (la), as set forth above, or from any combination of embodiments of the compound of formula (la), as set forth above, or the compound of formula (I) therein is selected from any one embodiment of the compound of formula (lb), as set forth above, or from any combination of embodiments of the compound of formula (lb), as set forth above.

Of the various aspects of methods of treating a disease or condition associated with Axl activity in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of formula (I), as set forth above in the Summary of the Invention, certain embodiments are preferred.

One embodiment of these methods is the method wherein the disease or condition is selected from the group consisting of rheumatoid arthritis, vascular disease, vascular injury, psoriasis, visual Impairment due to macular degeneration, diabetic retinopathy, retinopathy of prematurity, kidney disease, osteoporosis, osteoarthritis and cataracts.

One embodiment of these methods is the method wherein a manifestation of the disease or condition is solid tumor formation in said mammal.

One embodiment of these methods is the method wherein the disease or condition is selected from the group consisting of breast carcinoma, renal carcinoma, endometrial carcinoma, ovarian carcinoma, thyroid carcinoma, non-small cell lung carcinoma, and uveal melanoma.

One embodiment of these methods is the method wherein a manifestation of the disease or condition is liquid tumor formation in said mammal.

One embodiment of these methods is the method wherein the disease or condition is myeloid leukemia or lymphoma.

One embodiment of these methods is the method wherein the disease or condition is endometriosis.

One embodiment of these methods is the method wherein the compounds of formula (I) utilized therein is selected from any one embodiment of the compound of formula (la), as set forth above, or from any combination of embodiments of the compound of formula (la), as set forth above, or the compound of formula (I) therein is selected from any one embodiment of the compound of formula (lb), as set forth above, or from any combination of embodiments of the compound of formula (lb), as set forth above.

Another embodiment of the invention are those methods of treating a disease or condition associated with Axl activity by administering to the mammal a therapeutically effective amount of a pharmaceutical composition of the invention, as set forth above in the Summary of the Invention, wherein the disease or condition is selected from the group consisting of rheumatoid arthritis, vascular disease / injury (including but not limited to restenosis, atherosclerosis and thrombosis), psoriasis, visual impairment due to macular degeneration, diabetic retinopathy or retinopathy of prematurity, kidney disease (including but not limited to glomerulonephritis, diabetic nephropathy and renal transplant rejection), osteoporosis, osteoarthritis and cataracts.

Another embodiment of the invention are those methods of treating a disease or condition associated with Axl activity by administering to the mammal a therapeutically effective amount of a pharmaceutical composition of the invention, as set forth above in the Summary of the Invention, wherein the disease or condition is selected from the group consisting of breast carcinoma, renal carcinoma, endometrial carcinoma, ovarian carcinoma, thyroid carcinoma, non-small cell lung carcinoma, melanoma, prostate carcinoma, sarcoma, gastric cancer, uveal melanoma, myeloid leukemia and lymphoma.

Another embodiment of the invention are those methods of treating a disease or condition associated with Axl activity by administering to the mammal of therapeutically effective amount of a pharmaceutical composition of the invention, as set forth above in the Summary of the Invention, wherein the disease or condition is endometriosis.

It is understood that any embodiment of the compounds of formula (I), as set forth above, and any specific substituent set forth herein for a R1, R2, R3, R4 and R5 group in the compounds of formula (I), as set forth above, may be independently combined with other embodiments and/or substituents of compounds of formula (I) to form embodiments of the inventions not specifically set forth above. In addition, in the event that a list of substitutents is listed for any particular R group in a particular embodiment and/or claim, It is understood that each individual substituent may be deleted from the particular embodment and/or claim and that the remaining list of substituents will be considered to be within the scope of the invention.

Specific embodiments of the invention are described in more detail below in the following sections.

UTILITY AND TESTING OF THE COMPOUNDS OF THE INVENTION

The oncogenic RTK, Axl, was recently identified, using a retroviral-based functional genetic screening protocol, as a regulator of haptotactic migration, which is a key event in angiogenesis. Axl inhibition by RNAi-mediated silencing blocked endothelial cell migration, proliferation and in vitro tube formation. These observations, which were disclosed at the American Association Cancer Research General Meeting, April 16-20, 2005, Anaheim, California, and The 7th Annual Symposium on Anti-Angiogenic Agents, February 10-13, 2005, San Diego, California; (Requirement for The Receptor Tyrosine Kinase Axl in Angiogenesis and Tumor Growth, Holland, S.J. Powell, M.J., Franci, C., Chan, E., Friera, A.M., Atchison, R., Xu, W., McLaughlin, J., Swift,S.E., Pali, E„ Yam, G., Wong, S., Xu, X., Hu, Y., Lasaga, J., Shen, M., Yu, S., Daniel, R„ Hitoshi, Y., Bogenberger, J., Nor, J.E., Payan, D.G and Lorens, J.B), were substantiated by an in vivo study which demonstrated that stable, shRNAi-mediated Axl knockdown impaired formation of Junctional human blood vessels In a mouse model of human angiogenesis. These observations were published in a peer reviewed journal (Holland SJ, Powell MJ, Franci C, Chan EW, Friera AM, Atchison RE, McLaughlin J, Swift SE, Pali ES, Yam G, Wong S, Lasaga J, Shen MR, Yu S, Xu W, Hitoshi Y, Bogenberger J, Nor JE, Payan DG, Lorens JB. “Multiple roles for the receptor tyrosine kinase axl in tumor formation.” Cancer Res. (2005) Vol 65 pp 9294-303. These observations are also disclosed in U.S. Published Patent Application 2005/0118604 and European Patent Application 1 563 094, the disclosures of which are incorporated in full by reference. Axl signaling, therefore, impacts multiple functions required for neovascularization in vitro, and regulates angiogenesis in vivo. Regulation of these pro-anglogenic processes required the catalytic activity of Axl. Thus, Axl-mediated angiogenic stimulation would be amenable to modulation by a small molecule inhibitor of Axl catalytic activity.

Accordingly, the compounds of the invention are small molecule inhibtiors of Axl catalytic activity, and are therefore useful in treating diseases and conditions which are associated with Axl catalytic activity including those diseases and conditions which are characterized by angiogenesis and/or cell proliferation. In particular, the compounds of the invention and pharmaceutical compositions of the invention are useful in treating diseases and conditions which are alleviated by the modulation of Axl activity. For purposes of this invention, diseases and condtions which are alleviated by the "modulation of Axl activity" includes diseases and conditions which are alleviated by a decrease in Axl activity and diseases and conditions which are alleviated by an increase in Axl activity. Preferably such diseases and conditions are alleviated by a decrease in Axl activity. Diseases and conditions which are alleviated by the modulation of Axl activity include, but are not limited to, solid tumors, including, but not limited to, breast, renal, endometrial, ovarian, thyroid, and non-small cell lung carcinoma, melanoma, prostate carcinoma, sarcoma, gastric cancer and uveal melanoma; liquid tumors, including but not limited to, leukemias (particularly myeloid leukemias) and lymphomas; endometriosis, vascular disease / injury (including but not limited to restenosis, atherosclerosis and thrombosis), psoriasis; visual impairment due to macular degeneration; diabetic retinopathy and retinopathy of prematurity; kidney disease (including but not limited to glomerulonephritis, diabetic nephropathy and renal transplant rejection), rheumatoid arthritis; osteoarthritis, osteoporosis and cataracts.

In addition to the foregoing, the compounds of the invention are useful in treating diseases and conditions which are affected by the following biological processes: Invasion, migration, metastasis, or drug resistance as manifested in cancer; stem cell biology as manifested in cancer; invasion, migration, adhesion, or angiogenesis as manifested in endometriosis; vascular remodeling as manifested in cardiovascular disease, hypertension or vascular injury; bone homeostatasis as manifested in osteoporosis or osteoarthritis; viral infection as manifested, for example, in ebola virus infection; or differentiation as manifested in obesity. The compounds of the invention may also be used to modulate inflammatory processes by treating sepsis, acting as vaccine adjuvants, and/or potentiating the immune response in immuno-compromised patients.

The following animal models provide guidance to one of ordinary skill in the art in testing the compounds of the invention for their use in treating the disease or condition indicated.

The compounds of the invention may be tested for their use in treating leukemias and lymphomas bytesting the compounds In the xenograft in SCID mouse model using human Axl-expresing cancer cell lines including, but not limited to, HeLa, MDA-MB-231, SK-OV-3, OVCAR-8, DU145, H1299, ACHN, A498 and Caki-1.

The compounds of the invention may be tested for their use in treating leukemias in the xenograft in SCID or nu/nu mouse model using human Axl-expressing AML and CML leukemia cell lines.

The compounds of the invention may be tested for their use in treating endometriosis by using the syngenic mouse model of endometriosis (see Somigliana, E. et al., "Endometrial ability to implant in ectopic sites can be prevented by interleukin-12 in a murine model of endometriosis", Hum. Reprod. (1999), Vol. 14, NO. 12, pp. 2944-50). The compounds may also be tested for their use in treating endometriosis by using the rat model of endometriosis (see Lebovic, D.l. eta!., "Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis", Fartil. Steril. (2004), 82 Suppl 3, pp. 1008-13).

The compounds of the invention may be tested for their use in treating restenosis by using the balloon-injured rate carotid artery model (see Kim, D.W. etal., "Novel oral formulation of paclitaxel inhibits neointimal hyperplasia in a rat carotid artery injury model", Circulation (2004), Vol. 109, No. 12, pp. 1558-63, Epub 2004 Mar 8).

The compounds of the invention may also be tested for their use in treating restenosis by using the percutaneous transluminal coronary angioplasty in apoE deficient mouse model (see von der Thusen, J.H. et al., "Adenoviral transfer of endothelial nitric oxide synthase attenuates lesion formation in a novel murine model of postangioplasty restenosis", Arterioscler. Thromb. Vase. Biol. (2004), Vol. 24, No. 2, pp. 357-62).

The compounds of the invention may be tested for their use in treating atherosclerosis/thrombosis in the ApoE deficient mouse model (see Nakashima, Y. et al., "ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree", Arterioscler. Thromb. (1994), Vol. 14, No. 1, pp. 133-40).

The compounds of the invention may also be tested for their use in treating thrombosis using the collagen-epinephrin-induced pulmonary thromboembolism model and the stasis induced venous thrombosis model (see Angelillo-ScherrerA. etal., “Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy”, J Clin Invest. (2005) Vol 115 pp237-46).

The compounds of the invention may be tested for their use in treating psoriasis by using the SCID mouse model or the human skin model of psoriasis (see Nlckoloff, B.J. et al., "Severe combined immunodeficiency mouse and human psoriatic skin chimeras. Validation of a new animal model", Am. J. Pathol. (1995), Vol. 146, No. 3, pp. 580-8).

The compounds of the invention may be tested for their use in treating age-related macular degeneration or diabetic retinopathy by using the rat comeal angiogenesis model (see Sarayba MA, Li L, Tungsiripat T, Liu NH, Sweet PM, Patel AJ, Osann KE, Chittiboyina A, Benson SC, Pershadsingh HA, Chuck RS. Inhibition of corneal neovascularization by a peroxisome proliferator-activated receptor-gamma ligand. Exp Eye Res. 2005 Mar;80(3):435-42) or the laser-induced mouse choroidal neovasculation model (see Bora, P.S., et a!., "Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration", Proc. Natl. Acad. Sci. U. S. A. (2003), Vol. 100, No. 5, pp. 2679-84, Epub 2003 Feb 14).

The compounds of the invention may be tested for their use in treating retinopathy of prematurity in the mouse retinopathy of prematurity model (see Smith, L.E. eta!., "Oxygen-induced retinopathy in the mouse", Invest. Ophthalmol. Vis. Sci. (1994), Vol. 35, No. 1, pp. 101-11).

The compounds of the invention may be tested for their use in treating glomerulonephritis or diabetic nephropathy in the rat anti-Thy1.1-induced experimental mesengial proliferative glomerulonephritis model (see Smith, L.E. et al. cited above).

The compounds of the invention may be tested for their use in treating renal tranplant rejection by using a rat model of chronic renal transplant rejection (see Yin, J.L. et al., "Expression of growth arrest-specific gene 6 and its receptors in a rat model of chronic renal transplant rejection", Transplantation (2002), Vol. 73, No. 4, pp. 657-60).

The compounds of the invention may be tested for their use in treating rheumatoid arthritis by using the CAIA mouse model (see Phadke, K. et al., "Evaluation of the effects of various anti-arthritic drugs on type II collagen-induced mouse arthritis model", Immunopharmacology (1985),Vol. 10, No. 1, pp. 51-60).

The compounds of the invention may be tested for their use in treating osteoarthritis by using the STR/ORT mouse model (see Brewster, M. ef al., "Ro 32-3555, an orally active collagenase selective inhibitor, prevents structural damage in the STR/ORT mouse model of osteoarthritis", Arthritis. Rheum. (1998), Vol. 41, No. 9, pp. 1639-44).

The compounds of the invention may be tested for their use in treating osteoporosis by using the ovariectomized rat model (see Wronski, T.J. etal., “Endocrine and pharmacological suppressors of bone turnover protect against osteopenia in ovariectomized rats”, Endocrinology (1989), Vol. 125, no. 2, pp 810-6) or the ovariectomized mouse model (see Alexander, J.M. et al., “Human parathyroid hormone 1-34 reverses bone loss In ovariectomized mice", J Bone Miner Res. (2001), Vol. 16, no. 9, pp 1665-73; Fujioka, M. etal., “Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice”, JNutr. (2004), Vol. 134, no. 10, pp 2623-7).

The compounds of the invention may be tested for their use in treating cataracts by using the H202-induced model (see Kadoya, K. etal., "Role of calpain In hydrogen peroxide induced cataract", Cm. Eye Res. (1993), Vol. 12, No. 4, pp. 341-6) or the Emory mouse mode! (see Sheets, N.L. etal., "Cataract- and lens-specific upregulatlon of ARK receptor tyrosine kinase In Emory mouse cataract", Invest. Ophthalmol. Vis. Sci. (2002), Vol. 43, No. 6, pp. 1870-5).

PHARMACEUTICAL COMPOSITIONS OF THE INVENTION AND ADMINISTRATION

Administration of the compounds of the invention, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration of agents for serving similar utilities. The pharmaceutical compositions of the invention can be prepared by combining a compound of the invention with an appropriate pharmaceutically acceptable carrier, diluent or excipient, and may be formulated into preparations in solid, semi-solid, liquid or gaseous forms, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants, gels, microspheres, and aerosols. Typical routes of administering such pharmaceutical compositions include, without limitation, oral, topical, transderma!, inhalation, parenteral, sublingual, buccal, rectal, vaginal, and intranasal. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasterna! injection or infusion techniques. Pharmaceutical compositions of the invention are formulated so as to allow the active ingredients contained therein to be bioavailable upon administration of the composition to a patient. Compositions that will be administered to a subject or patient take the form of one or more dosage units, where for example, a tablet may be a single dosage unit, and a container of a compound of the invention in aerosol form may hold a plurality of dosage units. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington: The Science and Practice of Pharmacy, 20th Edition (Philadelphia College of Pharmacy and Science, 2000). The composition to be administered will, in any event, contain a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, for treatment of a disease or condition of interest in accordance with the teachings of this invention. A pharmaceutical composition of the invention may be in the form of a solid or liquid. In one aspect, the carriers) are particulate, so that the compositions are, for example, in tablet or powder form. The carrier(s) may be liquid, with the compositions being, for example, an oral oil, injectable liquid or an aerosol, which is useful in, for example, inhalatory administration.

When intended for oral administration, the pharmaceutical composition is preferably in either solid or liquid form, where semi-solid, semi-liquid, suspension and gel forms are included within the forms considered herein as either solid or liquid.

As a solid composition for oral administration, the pharmaceutical composition may be formulated into a powder, granule, compressed tablet, pill, capsule, chewing gum, wafer or the like form. Such a solid composition will typically contain one or more inert diluents or edible carriers. In addition, one or more of the following may be present: binders such as carboxymethylcellulose, ethyl cellulose, microcrystalline cellulose, gum tragacanth or gelatin; excipients such as starch, lactose or dextrlns, disintegrating agents such as alginic acid, sodium alginate, Primogel, corn starch and the like; lubricants such as magnesium stearate or Sterotex; giidants such as colloidal silicon dioxide; sweetening agents such as sucrose or saccharin; a flavoring agent such as peppermint, methyl salicylate or orange flavoring; and a coloring agent.

When the pharmaceutical composition is in the form of a capsule, for example, a gelatin capsule, it may contain, in addition to materials of the above type, a liquid carrier such as polyethylene glycol or oil.

The pharmaceutical composition may be in the form of a liquid, for example, an elixir, syrup, solution, emulsion or suspension. The liquid may be for oral administration or for delivery by injection, as two examples. When intended for oral administration, preferred composition contain, in addition to the present compounds, one or more of a sweetening agent, preservatives, dye/colorant and flavor enhancer. In a composition intended to be administered by injection, one or more of a surfactant, preservative, wetting agent, dispersing agent, suspending agent, buffer, stabilizer and isotonic agent may be Included.

The liquid pharmaceutical compositions of the invention, whether they be solutions, suspensions or other like form, may include one or more of the following adjuvants: sterile diluents such as water for injection, saline solution, preferably physiological saline, Ringer’s solution, isotonic sodium chloride, fixed oils such as synthetic mono or diglycerides which may serve as the solvent or suspending medium, polyethylene glycols, glycerin, propylene glycol or other solvents; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethyienediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. Physiological saline is a preferred adjuvant. An injectable pharmaceutical composition is preferably sterile. A liquid pharmaceutical composition of the invention intended for either parenteral or oral administration should contain an amount of a compound of the invention such that a suitable dosage will be obtained. Typically, this amount is at least 0.01% of a compound of the invention in the composition. When intended for oral administration, this amount may be varied to be between 0.1 and about 70% of the weight of the composition. Preferred oral pharmaceutical compositions contain between about 4% and about 75% of the compound of the Invention. Preferred pharmaceutical compositions and preparations according to the present invention are prepared so that a parenteral dosage unit contains between 0.01 to 10% by weight of the compound prior to dilution of the invention.

The pharmaceutical composition of the invention may be intended for topical administration, in which case the carrier may suitably comprise a solution, emulsion, ointment or gel base. The base, for example, may comprise one or more of the following: petrolatum, lanolin, polyethylene glycols, bee wax, mineral oil, diluents such as water and alcohol, and emulsifiers and stabilizers. Thickening agents may be present in a pharmaceutical composition for topical administration. If intended for transdermal administration, the composition may include a transdermal patch or iontophoresis device. Topical formulations may contain a concentration of the compound of the invention from about 0.1 to about 10% w/v (weight per unit volume).

The pharmaceutical composition of the invention may be intended for rectal administration, in the form, for example, of a suppository, which will melt in the rectum and release the drug. The composition for rectal administration may contain an oleaginous base as a suitable nonirritating excipient. Such bases include, without limitation, lanolin, cocoa butter and polyethylene glycol.

The pharmaceutical composition of the invention may include various materials, which modify the physical form of a solid or liquid dosage unit. For example, the composition may include materials that form a coating shell around the active ingredients. The materials that form the coating shell are typically inert, and may be selected from, for example, sugar, shellac, and other enteric coating agents.

Alternatively, the active ingredients may be encased in a gelatin capsule.

The pharmaceutical composition of the invention in solid or liquid form may include an agent that binds to the compound of the invention and thereby assists in the delivery of the compound. Suitable agents that may act in this capacity include a monoclonal or polyclonal antibody, a protein or a liposome.

The pharmaceutical composition of the invention may consist of dosage units that can be administered as an aerosol. The term aerosol is used to denote a variety of systems ranging from those of colloidal nature to systems consisting of pressurized packages. Delivery may be by a liquefied or compressed gas or by a suitable pump system that dispenses the active ingredients. Aerosols of compounds of the invention may be delivered In single phase, bi-phasic, or tri-phasic systems in order to deliver the active ingredient(s). Delivery of the aerosol includes the necessary container, activators, valves, subcontainers, and the like, which together may form a kit. One of ordinary skill in the art, without undue experimentation may determine preferred aerosols.

The pharmaceutical compositions of the invention may be prepared by methodology well known in the pharmaceutical art. For example, a pharmaceutical composition intended to be administered by injection can be prepared by combining a compound of the invention with sterile, distilled water so as to form a solution. A surfactant may be added to facilitate the formation of a homogeneous solution or suspension. Surfactants are compounds that non-covalently interact with the compound of the invention so as to facilitate dissolution or homogeneous suspension of the compound in the aqueous delivery system.

The compounds of the Invention, or their pharmaceutically acceptable salts, are administered in a therapeutically effective amount, which will vary depending upon a variety of factors including the activity of the specific compound employed; the metabolic stability and length of action of the compound; the age, body weight, general health, sex, and diet of the patient; the mode and time of administration; the rate of excretion; the drug combination; the severity of the particular disorder or condition; and the subject undergoing therapy. Generally, a therapeutically effective daily dose is (for a 70 kg mammal) from about 0.001 mg/kg (/'.e., 0.07 mg) to about 100 mg/kg (/.e., 7.0 gm); preferaby a therapeutically effective dose is (for a 70 kg mammal) from about 0.01 mg/kg (/.e., 0.7 mg) to about 50 mg/kg (/'.e., 3,5 gm); more preferably a therapeutically effective dose is (for a 70 kg mammal) from about 1 mg/kg (/.e., 70 mg) to about 25 mg/kg (/.e., 1.75 gm).

Compounds of the invention, or pharmaceutically acceptable salts thereof, may also be administered simultaneously with, prior to, or after administration of one or more other therapeutic agents. Such combination therapy includes administration of a single pharmaceutical dosage formulation which contains a compound of the Invention and one or more additional active agents, as well as administration of the compound of the invention and each active agent in its own separate pharmaceutical dosage formulation. For example, a compound of the invention and the other active agent can be administered to the patient together in a single oral dosage composition such as a tablet or capsule, or each agent administered in separate oral dosage formulations. Where separate dosage formulations are used, the compounds of the invention and one or more additional active agents can be administered at essentially the same time, i.e., concurrently, or at separately staggered times, i.e., sequentially; combination therapy is understood to include all these regimens.

PREPARATION OF THE COMPOUNDS OF THE INVENTION

The following Reaction Scheme illustrates methods to make compounds of this invention, i.e., compounds of formula (I):

(l) where R1, R2, R3, R4 and R5 are described above in the Summary of the Invention for compounds of formula (I), as isolated stereoisomers or mixtures thereof, or as pharmaceutically acceptable salts thereof. In particular, the following Reaction Scheme illustrates methods to make compounds of formula (la):

(la) where R1, R2, R3, R4 and R5 are as described above in the Summary of the Invention for compounds of formula (I), as isolated stereoisomers or mixtures thereof, or as pharmaceutically acceptable salts thereof, and methods to make compounds of formula (lb);

(lb) where R1, R2, R3, R4 and R5 are as described above in the Summary of the Invention for compounds of formula (I), as isolated stereoisomers or mixtures thereof, or as pharmaceutically acceptable salts thereof. It is understood that in the following Reaction Schemes, combinations of substituents and/or variables of the depicted formulae are permissible only if such contributions result In stable compounds.

It will also be appreciated by those skilled In the art that In the processes described below the functional groups of intermediate compounds may need to be protected by suitable protecting groups. Such functional groups include hydroxy, amino, mercapto and carboxylic acid. Suitable protecting groups for hydroxy include trialkylsilyl or diarylalkylsilyl (for example, f-butyldimethylsilyl, f-butyldiphenylsilyl or trimethylsilyl), tetrahydropyranyl, benzyl, and the like. Suitable protecting groups for amino, amidino and guanidino include benzyl, f-butoxycarbonyl, benzyloxycarbonyl, and the like.

Suitable protecting groups for mercapto include -C(0)-R" (where R" is alkyl, aryl or arylalkyl), p-methoxybenzyl, trityl and the like. Suitable protecting groups for carboxylic acids include alkyl, aryl or arylalkyl esters.

Protecting groups may be added or removed in accordance with standard techniques, which are known to one of ordinary skill in the art and as described herein.

The use of protecting groups is described in detail in Greene, T.W. and P.G.M. Wuts, Greene's Protective Groups in Organic Synthesis (1999), 3rd Ed., Wiley. As one of skill in the art would appreciate, the protecting group may also be a polymer resin such as a Wang resin, Rink resin or a 2-chlorotrityl-chloride resin.

It will also be appreciated by those skilled in the art, although such protected derivatives of compounds of this invention may not possess pharmacological activity as such, they may be administered to a mammal and thereafter metabolized in the body to form compounds of the invention which are pharmacologically active. Such derivatives may therefore be described as "prodrugs". All prodrugs of compounds of this invention are included within the scope of the invention.

It is understood that one of ordinary skill in the art would be able to make the compounds of the invention by methods similar to the methods described herein or by methods known to one of ordinary skill in the art. It is also understood that one of ordinary skill in the art would be able to make in a similar manner as described below other compounds of formula (I) not specifically illustrated below by using the appropriate starting components and modifying the parameters of the synthesis as needed. In general, starting components may be obtained from sources such as Sigma Aldrich, Lancaster Synthesis, Inc., Maybridge, Matrix Scientific, TCI, and Fluorochem USA, etc. or synthesized according to sources known to those skilled in the art (see, for example, Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th edition (Wiley, December 2000)) or prepared as described in this invention. 1H NMR spectra were recorded in CDCI3, DMSO-cfe, CD3OD, Acetone-db with trimethylsilane (TMS) as internal reference using Gemini 300 MHz instrument. Reagents and solvents were purchased from commercial sources and used without further purification. Flash column chromatography was conducted using silica gel (230-400 mesh) under a positive pressure of nitrogen. LCMS spectra for purity and mass were recorded using Waters LCMS instruments. Deionized water was used to dilute the reactions and wash the products. Brine used was prepared by dissolving sodium chloride into deionized water to saturation point.

Compounds of formula (la), as set forth below in Reaction Scheme 1 below, where R1, R2 and R3 are as defined above in the Summary of the Invention for compounds of formula (I) and R4 and Rs are hydrogen, are generally prepared as illustrated below in Reaction Scheme 1 where R1, R2 and R3 are as defined above in the Summary of the Invention for compounds of formula (I): REACTION SCHEME 1

Compounds of formula (A), formula (B) and formula (D) are commercially available or can be prepared by methods known to one skilled in the art or by methods disclosed herein.

In general, compounds of formula (la) are prepared, as set forth by Reaction Scheme 1, by first treating a compound of formula (A) (1.1 equiv) with an equivalent amount of an aniline of formula (B) in an polar solvent, including, but not limited to, isopropyl alcohol, at ambient temperatures overnight. The diarylisourea product of formula (C) generally precipitates and isolation can be accomplished via filtration, washing with an appropriate solvent, and drying. Hydrazine hydrate of formula (D) (2 equivalents) is added to a slurry of the compound of formula (C) in an alcohol or other appropriate solvent. Generally, the ring formation reaction occurs at ambient temperature and the product triazole of formula (la) can be isolated by standard isolation techniques. Compounds of formula (la) can be subsequently treated with an appropriately substituted alkylating or acylatlng agent under standard conditions to form compounds of formula (la) where R4 and R5 are as described above in the Summary of the Invention for compounds of formula (I).

Compounds of formula (lb) can be prepared using the synthetic route outlined in Reaction Scheme 1 in varying amounts depending on the steric and electronic nature of R1, R2 and R3 as well as the particular reaction conditions employed. In some instances, compounds of formula (lb) are isolated as minor isomers along with compounds of formula (la) as major isomers, e.g., during column chromatography as described herein.

Compounds of formula (C-1) are compounds of formula (C), as set forth above in Reaction Scheme 1, where R1 is hydrogen and R2 is 7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl, that is, where R2 has the following structure:

Compounds of formula (C-1) can be prepared according to the method described below in relation to Reaction Scheme 2: REACTION SCHEME 2

Compounds of formula (Ca) and formula (A) are commercially available or can be prepared according to methods described herein or known to one skilled in the art. Compounds of formula (Ba) are compounds of formula (B), as set forth above in Reaction Scheme 1.

In general, compounds of formula (C-1) are prepared, for example, as set forth above in Reaction Scheme 2, by nitration of the benzo[7]annulene of formula (Ca), followed by isolation of the ketone of formula (Cb1), for example, by crystallization. Reductive amination of the keto group in the ketone of formula (Cb1) yields the pyrrolidine-substituted compound of formula (Cc). Reduction of the nitro group of the pyrrolidine-substituted compound of formula (Cc), for example, by catalytic hydrogenation, gives the aniline of formula (Ba). Reaction of the aniline of formula (Ba) with, for example, diphenyl cyanocarbonimidate of formula (A), yields the compound of formula (C-1).

One aspect of the invention is a process for preparing an aryl-fused cycloheptanone or a heteroaryl-fused cycloheptanone of formula (i):

0)

J where is an aryl ring or a heteroaryl ring fused to the ring with the R12 substituents and each R12 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted aralkyl, and optionally substituted heteroarylalkyl. These compounds are useful as intermediates in the preparation of the compounds of the invention, and can be prepared as described below in REACTION SCHEME 2A wherein

is an aryl ring or a heteroaryl ring fused to the ring with the R12 substituents, each R12 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted aralkyl, and optionally substituted heteroarylalkyl, each R13 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl, and each LG is independently a suitable leaving group:

REACTION SCHEME 2A

(ii) (Hi) (i)

In this process, a reactant of formula (ii) is first combined with a reactant of formula (iii) in the presence of a protic solvent, an aprotic solvent, and a base to give an intermediate, for example, 8,9-dihydro-5H-benzo[7]annulen-7(6H)-one substituted at the 6-, 8-, or 6- and 8-positions or mixtures thereof with carboxy ester groups. Suitable leaving groups for this process include, but are not limited to, quaternary ammonium salts, alkyl or aryl sulfonates (e.g., methane sulfonate, tosylate, triflate), alkyl or aryl sulfides, phosphonates, and halogens (e.g., F, Cl, Br, I). In a specific embodiment, the leaving group LG is halogen. In a more specific embodiment LG is bromo. The intermediate, for example, 8,9-dihydro-5H-benzo[7]annulen-7(6H)-one, is then exposed to basic hydrolytic media followed by an acid to form compounds of formula (i). In some embodiments, the intermediate, for example, 8,9-dihydro-5H-benzo[7]annulen-7(6H)-one, is subjected to an acid media prior to exposure to the basic hydrolytic media. In some embodiments the intermediate, for example, 8,9-dihydro-5H-benzo[7]annulen-7(6H)-one, is subjected to an acid media and isolated prior to exposure to the basic hydrolytic media.

In some embodiments, is a phenyl ring, R13 is lower alkyl and R12 is hydrogen. Exemplary protic solvents include, but are limited to, alcohols, preferably alkanols, e.g., methanol, ethanol and the like. Exemplary aprotic solvents include, but are not limited to, ethers, e.g. THF, crown ethers and the like. In some embodiments, the aprotic and protic solvents are in about a 1:1 ratio by volume. Exemplary bases include, but are not limited to, metal alkoxides, e.g., lithium, sodium or potassium alkoxides. In one exemplary embodiment, the metal alkoxide is sodium methoxide. Exemplary acids and acidic media include inorganic and organic acids, typically diluted with water. Such inorganic and organic acids are described above in the Definitions section, under "pharmaceutically acceptable acid addition salt" and "pharmaceutically acceptable base addition salt". Exemplary basic hydrolytic media include, but are not limited to, alcoholic solutions of metal hydroxides or metal alkoxides. In some embodiments, the basic hydrolytic media includes an alcoholic solution of a metal hydroxide.

Preferably the combination of a reactant of formula (ii) with a reactant of formula (iii) In the presence of a protic solvent, an aprotic solvent, and a base process described above is performed within a temperature range of between about -10 °C and about 100 °C, more preferably within a temperature range of between about 0 °C and about 50 °C, even more preferably, within a temperature range of between about 0 °C and about 30 "C.

Preferably, exposure of the intermediate of the first step of the process to basic hydrolytic media followed by an acid to form compounds of formula (i) is performed within a temperature range of between about 40 °C and about 150 °C, more preferably within a temperature range of between about 60 °C and about 100 0C, even more preferably within a temperature range of between about 60 °C and about 100 °C.

Accordingly, an exemplary process for making the compound of formula (Ca), i.e., 8,9-dihydro-5H-benzo[7]annuien-7(6H)-one, as described above in Reaction Scheme 2, is described below in relation to REACTION SCHEME 2B.

REACTION SCHEME 2B

Dimethyl 3-oxopentanedioate and 1,2-bis(2-bromomethyl)benzene are commercially available, or can be prepared according to methods disclosed herein or methods known to one skilled in the art. The ester groups need not be methyl esters and the bromo groups need not be bromo groups in that any suitable leaving group will suffice. Also, as described above, the 3-oxopentanedioate may be substituted at the 2-and 4-positions as long as as one proton on each of the 2- and 4-positions exists given that at least one proton Is needed for the deprotonation and subsequent C-C bond formation with the carbon bearing the leaving group.

Accordingly, compounds of formula (Ca) are prepared, as set forth above in REACTION SCHEME 2B, by first combining a pentane-3-dioate, e.g. dimethyl 3-oxopentanedioate shown, with a 1,2-bismethyl aromatic having a suitable leaving group on each methyl group, e.g., 1,2-bis(bromomethyl)benzene, in a mixed protic/aprotic solvent medium, e.g., THF-MeOH, and a metal alkoxide, e.g., sodium methoxide. The metal alkoxide can be added as such or made in situ via careful addition (e.g., at low temperature) of the appropriate metal to at least the protic solvent, preferably prior to combination with the remaining reactants. The intermediate benzo[7]annulene product so formed can be optionally isolated and may contain one or two carboxy ester groups depending on the reaction conditions, e.g., methyl 7-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6,8-dicarboxylate, as shown above. The intermediate, dimethyl 7-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6,8-dicarboxylate, is subjected to basic hydrolysis (saponfication) conditions followed by acidification to give compounds of formula (Ca).

All compounds of the invention which exist in free base or acid form can be converted to their pharmaceutically acceptable salts by treatment with the appropriate inorganic or organic base or acid by methods known to one of ordinary skill in the art.

Salts of the compounds of the invention can be converted to their free base or acid form by standard techniques known to one skilled in the art.

The following specific Synthetic Examples are provided as a guide to assist in the practice of the invention, and are not intended as a limitation on the scope of the invention. The number following each compound below refers to its number in Tables 1-7, as discussed in more detail below. SYNTHETIC EXAMPLE 1

Synthesis of 1 -(5l6-Dihydnobenzo[h]quinazolin-2-yl)-/V3-(4-(4-methylpiperazin-1 -yl)phenyl)-1H-1,2,4-triazole-3,5-diamine

A. Synthesis of 5.6-Dihvdrobenzorhlauinazolin-2-amine

α-Tetralone (5.00 g, 34.2 mmol) was heated with t-butoxy bis(dimethylamino)methane (5.96 g, 34.2 mMol) at 90 °C overnight. The solvent was removed under vacuum to give a brown oil. The oil was dissolved in anhydrous ethanol (80 mL) and treated with guanidine hydrochloride (6.53 g, 68.4 mmol) and sodium metal (1.64 g, 71.3 mmol). After the sodium dissolved, the mixture was heated under reflux for 46 h. The mixture was cooled to ambient temperature and guanidine hydrochloride (1.00 g) and sodium metal (0.4 g) were added. Heating was then continued for 24 h. The solvent was removed under vacuum. The residue was partitioned between chloroform and water. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was crystallized from ethanol to give 5,6-dihydrobenzo[h]qulnazolin-2-amine as brown needles, 3.07 g; 1H NMR (DMSO-ds, 300 MHz) 8.08 (m, 2H), 7.24-7.40 (m, 3H), 6.40 (s, 1H), 2.81 (m, 2H), 2.68 (m, 2H) ppm; 13C-NMR (DMSO-ofe, 75 MHz) 163.60, 159.09,157.54, 140.14,133.22, 131.02, 128.80, 127.37,125.16, 117.15, 28.46, 23.80; MS (ES) 198 (M+H). B. Synthesis of 5.6-Dihvdrobenzoi/?1auinazolin-2(3HVone

5.6- Dihydrobenzo[ft]quinazolin-2-amine (3.07 g) was heated under reflux with 120 mL of 50% aqueous hydrochloric acid. The solvent was removed under vacuum to give 5,6-dihydrobenzo[ft]quinazolin-2(3H)-one as a tan solid, 2.97 g; 1H NMR (DMSO-cfe> 300 MHz) 8.16 (d, 1H), 8.08 (s, 1H), 7.50 (t, 1H), 7.35 (m, 2H), 2.88 (m, 2H), 2.70 (m, 2H) ppm; 13C NMR (DMSO-c/e, 75 MHz) 164.86,155.14, 148.28,142.07, 133.49, 130.30, 129.23, 127.73,127.01, 112.91,28.26, 23.37; MS (ES) 199 (M+H). C. Synthesis of 2-Chloro-5.6-dihvdrobenzortflauinazoline

5.6- Dihydrobenzo[/?]qulnazolln-2(3H)-one (2.97 g) was heated at 100 °C in phosphorus (III) oxychloride (70 mL) for 2 h. The solvent was removed under vacuum and the residue was treated with ice, followed by 1 M aqueous potassium carbonate solution. The aqueous solution was extracted with a mixture of ether and ethyl acetate, dried over anhydrous sodium sulfate and concentrated under vacuum to give 2-chloro- 5,6-dihydrobenzo[ft]quinazoline as a yellow solid; 1H NMR (CDCl3/MeOD4, 300 MHz) 8.86 (s, 1H), 8.16 (m, 1H), 7.25-7.35 (m, 2H), 7.15 (m, 1H), 2.85 (m, 4H) ppm; 13C NMR (CDCI3/MeOD4, 75 MHz ) 162.83,159.45, 157.40, 139.60, 132.35, 130.99, 128.38, 127.61,127.20, 126.14, 27.39, 24.11; MS (ES) 217/219 (M+H). D. Synthesis of 2-Hvdrazinvl-5.6-dlhvdrobenzof/?lauinazoline

Crude 2-chloro-5,6-dihydrobenzo[fj]quinazoline was heated at 120 °C in a mixture of anhydrous pyridine (20 mL) and anhydrous hydrazine (7 mL) for 4 h. The solvent was removed under vacuum and the residue was partitioned between chloroform and 1M aqueous potassium carbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to give 2-hydrazinyl-5,6-dihydrobenzo[fj]quinazollne as a white solid, 2.16 g. 1H NMR (CDCI3, 300 MHz) 8.27 (d, 1H), 8.20 (s, 1H), 7.35 (m, 2H), 7.21 (d, 1H), 6.42 (s, 1H), 4.00 (br s, 2H), 2.91 (m, 2H), 2.80 (m, 2H) ppm; 13C NMR (CDCI3, 75 MHz) 164.29,160.00,156.72, 139.87, 132.83, 131.02, 128.25, 127.25, 125.47, 119.03, 28.54, 24.24; MS (ES) 213 (M+H). E. Synthesis of l-(5.6-Dihvdrobenzorfflauiriazolin-2-vl)-/V3-(4-f4-methvlpiperazin-1- vlbhenvl)-1 /-/-1.2.4-triazole-3.5-diamlne 2-Hydrazinyl-5,6-dihydrobenzo[ft]quinazoline (40 mg, 0.19 mmol) and (Z)-phenyl A/,-cyano-W-(4-(4-methylpiperazin-1-yl)phenyl)carbamimidate (67 mg, 0.20 mMol) were suspended in isopropanol and subjected to microwave irradiation (150 °C, 20 min). A precipitate formed in the microwave vial. After further cooling at -20 °C, the solid was filtered off, washed with cold isopropanol and dried under vacuum to give 1-(5,6-dihydrobenzo[h]quinazolin-2-yl)-A/3-(4-(4-methylpiperazin-1-yl)phenyl)-1/V-1,2,4-triazole- 3,5-diamine, compound #92, 32 mg; 1H NMR (DMSO-of6, 300 MHz) 8.76 (s, 1H), 8.65 (s, 1H), 8.16 (d, 1H), 7.65 (s, 2H), 7.46-7.53 (m, 4H), 7.37 (m, 1H), 6.84 (d, 2H), 2.90-3.05 (m, 8H), 2.48 (m, 4H), 2.22 (s, 3H) ppm; MS (ES) 454.17 (M+H). SYNTHETIC EXAMPLE 2

Synthesis of HS.e-Dihydrobenzot^cinnolin-S-yO-A/^S-fluoro^-^-ipyrrolidin-l-yl)piperidin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine

A. Synthesis of 5.6-Dihvdrobenzof/?1cinnolin-3<'2H)-one

α-Tetralone (6.00 g, 40 mmol) and glyoxylic acid monohydrate (4.08 g, 44 mmol) were cooled on an ice-water bath. A solution of sodium hydroxide (4.92 g, 123 mmol) in water (100 mL) was added. The ice bath was then removed and the reaction mixture stirred for 0.5 h. The mixture was extracted with diethyl ether (discarded). The aqueous layer was then cooled on ice and acidified with concentrated hydrochloric acid. The white solid which precipitated was filtered off, washed well with water and air dried. The solid was then heated under reflux with hydrazine monohydrate (20 mL) for 0.5 h. After cooling, the precipitated solid was filtered off, washed with ethanol and dried under vacuum to give 5,6-dihydrobenzo[/?]cinnolin-3(2H)-one as a pale yellow solid, 4.5 g; 1H NMR (DMSO-cfe, 300 MHz) 12.93 (s, 1H), 7.88 (m, 1H), 7.29 (m, 3H), 6.75 (s, 1H), 2.82 (m, 4H) ppm; 13C NMR (DMSO-cf6, 75 MHz) 161.30, 144.74,141.64, 138.24,131.00, 129.83, 128.96, 127.77,126.01,124.01, 28.48, 27.48; MS (ES) 199 (M+H). This procedure is similar to the procedure described in S. Villa et. at, J. Heterocyclic Chem., 36, 485 (1999). B. Synthesis of 3-Chloro-5.6-dihvdrobenzoihicinnollne

5,6-Dihydrobenzo[/7]cinnolin-3(2H)-one (4.5 g) was heated at 100 °C with phosphorus (III) Oxychloride (80 mL) for 6.5 h. The solvent was removed under vacuum and the residue was treated with ice water. The resulting solid was filtered off, washed well with water and air dried to give 3-chloro-5,6-dihydrobenzo/lh]cinnoline; 1H NMR (DMSO-d6l 300 MHz) 8.32 (m, 1H). 7.36 (s, 1H), 7.32 (m, 2H), 7.19 (d, 1H), 2.91 (s, 4H) ppm; MS (ES) 217/219 (M+H). C. Synthesis of 3-Hvdrazinvl-5.6-dihvdrobenzof/7lcinnoline

3-Chloro-5,6-dihydrobenzo[/7]cinnoline was heated at 100 °C in a mixture of anhydrous pyridine (30 mL) and anhydrous hydrazine (5 mL) for 3.25 h. The solvent was removed under vacuum and the residue was partitioned between chloroform and 1M aqueous potassium carbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was triturated with diethyl ether and filtered to give 3-hydrazinyl-5,6-dihydrobenzo[/?]cinnoline as a beige solid; 1H NMR(DMSO-c/e, 300 MHz) 8.17(d, 1H), 7.91 (brs, 1H), 7.28 (m, 3H), 6.87 (s, 1H), 4.34 (br s, 2H), 2.92 (m, 4H) ppm; 13C NMR (DMSO-cfe, 75 MHz) 162.49,147.92,137.95, 137.39,132.97,128.87, 128.75, 127.56, 123.59,110.55,28.01, 27.66; MS(ES)213 (M+H). D. Synthesis of 1-(5.6-Dihvdrobenzof/?lcinnolin-3-vh-A/3-(3-fluoro-4-r4-(Dvrrolidin-1- vl k)iperidin-1-vlk)henvlt-1H-1.2.4-triazole-3.5-diamine 3-Hydrazinyl-5,6-dihydrobenzo|/j]cinnoline (51 mg, 0.24 mMol) and (Z)-phenyl N'-cyano-/V-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)carbamimidate (98 mg, 0.24 mMol) were suspended in isopropanol (3 mL) and subjected to microwave irradiation (150 °C, 20 min). The crude product was purified by radial chromatography on silica gel, eluting with 95% dichloromethane and 5% 2M ammonia in methanol to give 1-(5,6-dihydrobenzo[/7]cinnolin-3-yl)-W3-(3-fluoro-4-(4-(pyrrolidin-1 -yl)piperidin-1 -yl)phenyl)-1 H- 1,2,4-triazole-3,5-diamine, compound #170; 1H NMR (CDCl3/MeOD4, 300 MHz) 10.84 (s, 1H), 8.43 (d, 1H), 7.75 (s, 1H), 7.61 (d, 1H), 7.41 (m, 2H), 7.26 (m, 2H). 6.93 (t, 1H), 3.42 (m, 2H), 3.00 (m, 3H), 2.60-2.75 (m, 6H), 2.15 (m, 1H), 1.98 (m, 2H), 1.74-1.95 (m, 7H) ppm; MS (ES) 526.43 (M+H). SYNTHETIC EXAMPLE 3

Synthesis of A/3-(4-(4-((1S,2S,4R)-bicyclot2.2.1]heptan-2-yl)piperazin-1 -yl)phenyl)-1-(2-chloro-7-methylthieno[3l2-c/]pyrimidin-4-yl)-1H-1l2l4-triazole-3l5-diamine

A. Synthesis of (+W1S. 4f?1-Norcamphor

To a stirred solution of (+)-enc/o-Norborneol (3.4 g; 30.30 mmol; 1.0 equiv) and 3 g of Molucular Sieves (4 A) in 100 mL of anhydrous methylene chloride was added pyridinium chlorochromate (9.8 g; 45.47 mmol; 1.5 equiv) in small portions. The reaction was stirred at 0 °C for 2 hours. Then ether was added and the solution was filtered through a celite pad. The celite was washed with ether (3X), The organic solutions were combined, dried over MgS04l filtered and evaporated to give (+)-(1 S, 4R)-norcamphor in quantitative yield; 1H-NMR (CDCI3, 300 MHz) 2.64 (d, J = 19.8 Hz, 2H), 2.10-2.05 (m, 2H), 1.88-1.72 (m, 3H), 1.57-1.41 (m, 3H) ppm. B. Synthesis of 1 -Bicvclor2.2.11hept-2-vl-4-f4-nitrophenvlfoiperazine 1-(4-Nitrophenyl)piperazine (6.28g; 30.3 mmol; 1.0 equiv) was dissolved in 60 mL of anhydrous dichloroethane, followed by the addition of (+)-(1 S, 4R)-norcamphor, glacial acetic acid (3.47 mL; 60.6 mmol; 2.0 equiv) and NaBH(OAc)3 (9.0 g; 42.42 mmol; 1.4 equiv). The flask was flushed with N2 and allowed to stir at ambient temperature overnight. The reaction mixture was diluted with methylene chloride and washed with saturated NaHC03, The organic layer was dried over MgS04 and evaporated to give 1-blcyclo[2.2.1]hept-2-yl-4-(4-nitrophenyl)piperazine as a yellow solid (9.0 g; 98% yield); 1H-NMR (DMSO-c/e, 300 MHz) 8.02 (d, J = 9.3 Hz, 2H), 6.99 (d, J = 9.3 Hz, 2H), 3.45- 3.38 (m, 4H), 2.42-2.36 (m, 4H), 2.29-2.15 (m, 3H), 1.80-1.60 (m, 2H), 1.56-1.40 (m, 1H), 1.36-1.14 (m, 4H), 0.90-0.86 (m, 1H) ppm; MS (ES) 302.64 (M+H). C. Synthesis of 1-Bicvclof2.2.11heDt-2-vl-4-(4-aminophenvhDiperazine

To a suspension of (3.0 g; 9,95 mmol) in MeOH (100 mL) was added 10% Pd/C. The reaction was shaken under H2 (40-50 psi) at ambient temperature for 2 hours and then filtered through a celite pad. The celite was washed with MeOH. The filtrate was concentrated in vacuo to give 1-bicyclo[2.2.1]hept-2-yl-4-(4-aminophenyl)piperazine as a tan solid (quantitative yield); 1H-NMR (DMSO-c/e, 300 MHz) 6.64 (d, J = 8.7 Hz, 2H), 6.45 (d, J = 8.7 Hz, 2H), 4.53 (br. s, 2H), 2,88 (t, J = 4.2 Hz, 4H), 2.39 (t, J= 4.2 Hz, 4H), 2.27-2.13 (m, 3H), 1.75-1.61 (m, 2H), 1.50-1.47 (m, 1H), 1.35-1.12 (m, 4H), 0.87-0.83 (m, 1H) ppm; MS (ES) 272.18 (M+H). D. Synthesis of A/-Cvano-/y-f4-r4-(bicvclof2.2.11heDt-2-vO-1 -piperazinvllPhenvl)-0- phenvlisourea A mixture of 1-bicyclo[2.2.1]hept-2-yl-4-(4-aminophenyl)piperazine (2.0 g; 7.4 mmol; 1.0 equiv) and diphenyl cyanocarboimidate (1.76 g; 7.4 mmol; 1.0 equiv) in 20 mL of /sopropanol was stirred at ambient temperature overnight. The solid was filtered, washed with /'sopropanol and dried to give /V-cyano-AT-{4-[4-(1-bicyclo[2.2.1]hept-2-yl)-1-piperazinyl]phenyl)-0-phenylisourea as a pale-pink solid (2.84 g, 92% yield). 1H-NMR (DMSO-de, 300 MHz) 10.56 (br. s, 1H), 7.41 (t, J= 6.0 Hz, 2H), 7.26-7.21 (m, 5H), 6.90 (d, J= 6.9 Hz, 2H), 3.15-3.05 (m, 4H), 2.45-2.34 (m, 4H), 2.29-2.14 (m, 3H), 1.78-1.62 (m, 2H), 1.50-1.40 (m, 1H), 1.36-1.17 (m, 4H), 0.89-0.86 (m, 1H) ppm; MS (ES) 416.55 (M+H), 414.24 (M-H). E. Synthesis of 2-Chloro-4-hvdrazino-7-methvlthienor3.2-dlpyrimidine

Hydrazine monohydrate (2.21 mL; 45.6 mmol; 2.0 equiv) was added to a suspention of 2,4-dichloro-7-methylthieno[3,2-d]pyrimidine (5 g; 22.8 mmol; 1.0 equiv) in 40 mL of EtOH. The reaction was stirred at ambient temperature for 2 days. The solid was filtered, washed with H20 and dried to give 2-chloro-4-hydrazino-7-methylthieno[3,2-d]pyrimidine as an off-white solid (4.4 g; 90% yield); MS (ES) 214.97 (M+H), 212.99 (M-H). F. Synthesis of /^-(4-(4-((1 S.2S.4ffl-bicvclof2.2.nheDtan-2-vltoiperazin-1 - vltohenvO-1 -(2-chloro-7-methvlthienor3.2-cflpvrimidin-4-vl'l-1 H-1.2.4-triazole-3.5-diamine A mixture of W-cyano-W-{4-[4-(bicyclo[2.2.1]hept-2-yl)-1-piperazinyl]phenyl}-0-phenylisourea (50 mg; 0.12 mmol; 1.0 equiv) and 2-chloro-4-hydrazino-7-methylthieno[3,2-d]pyrimidine (26 mg; 0.12 mmol; 1 equiv) in 0.5 mL of NMP was heated in the microwave apparatus at 180 °C for 6 min. Purification by HPLC gave /^-(4-(4-((1 S,2S,4R)-bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1-(2-chloro-7-methylthieno[3,2-af]pyrimidin-4-yl)-1H-1,2,4-triazole-3,5-diamine formic acid, compound #139, as a yellow solid (20 mg; 31% yield); 1H-NMR (DMSO-d6, 300 MHz) 9.20 (br. s, 1H), 8.21 (s, 1H), 7.90 (br. s, 2H), 7.56 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.7 Hs, 2H), 3.10-3.02 (m, 4H), 2.45-2.40 (m, 4H), 2.30-2.15 (m, 3H), 1.78-1.62 (m, 2H), 1.50-1.40 (m, 1H), 1.37-1.14 (m, 4H), 0.90-0.86 (m, 1H) ppm; MS (ES) 536.19 (M+H), 534.26 (ΜΗ). SYNTHETIC EXAMPLE 4

In a similar manner as described above utilizing the appropriately substituted starting materials, the following compounds of the invention were prepared: 1 -phenyl-/V3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #1, pale-yellow solid; MS (ES) 379.67 (M+H), 377.54 (M-H); 1-phenyl-/V5-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #2, yellow solid; MS (ES) 379.26 (M+H), 377.25 (M-H); 1-(4-isopropylphenyl)-/V3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #3, MS (ES) 421.47 (M+H), 419.46 (M-H); /^-( 3-chlo ro-4-( 2-( pyrrol i d i n-1 -yl )eth oxy) p henyl)-1 -(py ri d i n-2-yl)-1H-1,2,4-triazol e-3,5-diamine, compound #4, white solid; 1H NMR (DMSO-de, 300 MHz) 9.10 (s, 1H), 8.40 (d, 1H), 8.19 (s, 1H), 7.99 (t, 1H), 7.80-7.60 (m, 3H), 7.42 (d, 1H), 7.20 (t, 1H), 7.03 (d, 1H), 4.08 (t, 2H), 2.82 (t, 2H), 2.61 (broad s, 4H), 1.75 (broad s, 4H) ppm; MS (ES) 402.48 (M+H), 397.92 (M-H); 1-(pyridin-2-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #5, white solid; 1H NMR (DMSO-de. 300 MHz) 8.86 (s, 1H), 8.40 (d, 1H), 8.20 (s, 1H), 7.91 (t, 1H), 7.64 (m, 2H), 7.57 (d, 2H), 7.20 (t, 1H), 6.83 (d, 1H), 4.00 (t, 2H), 2.81 (t, 2H), 2.60 (broad s, 4H), 1.71 (broad s, 4H) ppm; MS (ES) 366.62 (M+H); A/5-methyl-1-(pyridln-2-yl)-/V3-(4-(2-(pynOlidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5- diamine, compound #6, yellow solid; MS (ES) 380.59 (M+H); A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(4-(trifluoromethyl)pyrimidin-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #7, MS (ES) 435.00 (M+H), 433.15 (M-H); 4-(5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1 H-1,2,4-triazoM - yl)benzenesulfonamide, compound #8, MS (ES) 443.97 (M+H), 442.13 (M-H); A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(quinoxalin-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #9, MS (ES) 417.06 (M+H), 415.16 (M-H); 1-(2-chloropyridin-4-yl)-A/3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5- diamine, compound #10, pale-yellow solid; MS (ES) 414.46 (M+H), 412.44 (M-H); 1-(benzo[cflthiazol-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #11, MS (ES) 421.98 (M+H), 420.03 (M-H); 1-(6-chloropyridazln-3-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #12, MS (ES) 400.99 (M+H), 399.01 (M-H); 1 -(pyrazin-2-yl)-A/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #13, MS (ES) 367.05 (M+H), 365.17 (M-H); 1-(1-methyl-1 A7-benzo[c/]imidazol-2-yl)-A/3-(4-(2-(pyrrolidln-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #14, MS (ES) 419.09 (M+H), 417.24 (M-H); 1-(2-morpholinopyridin-4-yl )-/^-(4-(2-(piperidln-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #15, pale-yellow solid; MS (ES) 465.29 (M+H), 463.23 (M-H); 1 -(6-chloropyridin-2-yl)-A/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #16, MS (ES) 400.02 (M+H), 398.19 (M-H); 1-(5-chloropyridin-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #17, MS (ES) 399.99 (M+H), 397.94 (M-H); 1 -(3-chloropyridin-2-yl)-A/3-(4-(2-(pynrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #18, MS (ES) 400.02 (M+H); 1 -(6-chloropyridin-2-yl)-A/3-(4-(2-(piperidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #19, off-white solid; MS (ES) 414.15 (M+H), 412.00 (M-H); 1 -(6-morpholinopyridin-2-yl)-/V3-(4-(2-(piperidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #20, pale-brown solid; MS (ES) 465.50 (M+H); A/3-(4-(2-(2-methylpyrrolidin-1-yl)ethoxy)phenyl)-1-(quinoxalin-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #21, yellow solid; MS (ES) 431.25 (M+H), 429.20 (M-H); 1 -(benzo[cf]thiazol-2-yl)-A/3-(4-(2-(2-methylpyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #22, off-white solid; MS (ES) 436.16 (M+H), 434.13 (M-H); 1-(1-methyl-1H-benzo[cf]imidazol-2-yl)-A/3-(4-(2-(2-methylpyrrolidin-1-yl)ethoxy)phenyl)- 1 Η-1,2,4-triazole-3,5-diamine, compound #23, purple solid; MS (ES) 433.56 (M+H), 431.16 (M-H); 1 -(1 W-benzo[c(]imidazol-2-yl)-A/3-(4-(2-(2-methylpyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #24, purple solid; MS (ES) 419.50 (M+H), 417.21 (M-H); 1-(phthalazin-1-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #25, yellow foam; MS (ES) 417.09 (M+H), 414.97 (M-H); A/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 -(4-(trifluoromethyl)pyridin-2-yl)-1 H· 1,2,4- triazole-3,5-diamine, compound #26, white solid; 1H NMR (DMSO-of6, 300 MHz) 8.63 (d, 1H), 7.78 (d, 2H), 7.50 (m, 2H), 6.89 (d, 2H), 4.00 (t, 2H), 2.82 (t, 2H), 2.61 (m, 4H), 1.73 (broad s, 4H) ppm; MS (ES) 434.05 (M+H), 431.95 (M-H); 1-(2-fluorophenyl)-A/3-(4-(2-(2-methylpyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #27, pale-brown solid; MS (ES) 397.46 (M+H), 395.45 (M-H); 1 -(2-fluorophenyl)-A/3-(4-(2-(piperidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #28, off-white solid; MS (ES) 397.38 (M+H), 395.11 (M-H); A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(3-(trifluoromethyl)pyridin-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #29, MS (ES) 434.04 (M+H), 432.05 (M-H); 1-(6-methoxypyridin-2-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #30, MS (ES) 396.09 (M+H), 394.21 (M-H); 1-(1 H-benzo[c(]imidazol-2-yl)-Af3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole- 3.5- diamine, compound #31, MS (ES) 405.10 (M+H), 403.05 (M-H); 1-(5-bromopyridin-2-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5- diamine, compound #32, MS (ES) 445.97 (M+H); methyl 1-(2-(4-(5-amino-1-(quinoxalin-2-yl)-1H-1,2,4-triazol-3- ylamino)phenoxy)ethyl)pyrrolidine-2-carboxylate, compound #33, off white solid; 1H NMR (CD3OD, 300 MHz) 9.41 (s, 1H), 8.08 (m, 2H), 7.89 (m, 3H), 7.58 (d, 2H), 6.90 (d, 2H), 4.12 (m, 2H), 3.60 (s, 3H), 3.40 (m, 1H), 3.01 (m, 2H), 2.79 (m, 2H), 2.20 (m, 2H), 1.84 (m, 3H) ppm; MS (ES) 475.43 (M+H), 473.16 (M-H); 1-(2-fluorophenyl)-N3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #34, pale-brown solid; MS (ES) 383.40 (M+H), 381.12 (M-H); 1-(6-(methylamino)pyridin-2-yl)-/\/3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole- 3.5- diamine, compound #35, pale-yellow solid; MS (ES) 409.48 (M+H), 407.32 (M-H); 1-(6-(dimethylamino)pyridin-2-yl)-W3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1/-/-1,2,4- triazole-3,5-diamine, compound #36, pale-brown solid; MS (ES) 423.41 (M+H); 1 -(2-chloroquinazolin-4-yl)-/V3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 /7-1,2,4-triazole-3,5-diamine, compound #37, yellow solid; MS (ES) 451.50 (M+H), 449.38 (M-H); 1-(2-morpholinoquinazolin-4-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1/7-1,2,4-triazole- 3.5- diamine, compound #38, yellow solid; MS (ES) 502.41 (M+H), 500.33 (M-H); 1- (benzo[d]thiazol-2-yl)-A/3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1f/-1l2,4- triazole-3,5-diamine, compound #39, MS (ES) 456.06 (M+H), 454.20 (M-H); W3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(1-methyl-1/-/-benzo[d]imidazol-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #40, MS (ES) 453.14 (M+H), 451.22 (M-H); A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(quinolin-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #41, MS (ES) 416.48 (M+H), 414.41 (M-H); 2- (5-amino-3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenylamino)-1 /7-1,2,4-triazol-1 -yl)-6- methylpyrimidin-4-ol, compound #42, MS (ES) 397.15 (M+H), 395.25 (M-H); methyl 1 -(2-(4-(5-amino-1 -(benzo[dlthiazol-2-yl)-1 /7-1,2,4-triazol-3- ylamino)phenoxy)ethyl)pyrrolidine-2-carboxylate, compound #43, off white solid; MS (ES) 480.21 (M+H), 478.21 (M-H); 1 -(2-chloro-6,7-dimethoxyquinazolin-4-yl)-/\/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-l H- 1,2,4-triazole-3,5-diamine, compound #44, yellow solid; MS (ES) 511.17 (M+H), 509.18 (M-H); 1-(6,7-dimethoxyquinazolin-4-yl)-/\/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1/7-1,2,4- triazole-3,5-diamine, compound #45, yellow solid; MS (ES) 477.19 (M+H), 475.26 (M-H); A/3-(4-(2-(2,5-dimethylpyrrolidin-1 -y!)ethoxy)phenyl)-1 -(quinoxalin-2-yl)-1 /7-1,2,4-triazole- 3.5- diamine, compound #46, orange solid; MS (ES) 445.51 (M+H), 443.48 (ΜΗ); 1-(pyrimidin-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl )-1/7-1,2,4-triazole-3,5-diamine, compound #47, MS (ES) 367.14 (M+H); 1-(6-chloroquinazolin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1/7-1,2,4-triazole-3,5-dlamine, compound #48, yellow solid; MS (ES) 451.14 (M+H), 449.19 (M-H); 1-(2-chloro-6,7-dihydro-5/7-cyclopenta[c/|pyrimidin-4-yl)-/V3-(4-(2-(pyrrolidin-1- yl)ethoxy)phenyl)-1/7-1,2,4-triazole-3,5-diamine, compound #49, yellow solid; MS (ES) 441.11 (M+H), 439.24 (M-H); 1-(isoquinolln-1-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1/7-1,2,4-triazole-3,5-diamine, compound #50, yellow solid; MS (ES) 416.41 (M+H), 414.48 (M-H); W3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(thieno[2,3-c/lpyrimidin-4-yl)-1/7-1,2,4-triazole- 3.5- diamine, compound #51, pale-brown solid; MS (ES) 423.36 (M+H), 421.15 (M-H); 1-(6-phenylthieno[3,2-c(lpyrimidin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #52, yellow solid; MS (ES) 499.25 (M+H), 497.14 (M-H); /V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(2-(trifluoromethyl)quinazolin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #53, orange solid; MS (ES) 485.32 (M+H), 483.22 (M-H); /\/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(thieno[3,2-c(]pyrlmidin-4-yl)-1H-1,2,4-triazole- 3.5- diamine, compound #54, pale-yellow solid; MS (ES) 423.21 (M+H), 421.20 (M-H); /V3-(3-fluoro-4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 -(quinoxalin-2-yl)-1 H-1,2,4-triazoie-3,5-diamine, compound #55, yellow solid; MS (ES) 435.60 (M+H), 433.20 (M-H); 1-(benzo[cdthiazol-2-yl)-/V3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #56, off-white solid; MS (ES) 440.68 (M+H), 438.16 (M-H); /V3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(pyridin-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #57, pale-brown solid; MS (ES) 384.47 (M+H); W3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 -(isoquinolin-1 -yl)-1 H-1,2,4-triazole-3,5-diamine, compound #58, pale-yellow solid; MS (ES) 434.43 (M+H), 432.34 (M-H); /V3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1H- 1,2,4-triazole-3,5-diamine, compound #59, pale-yellow solid; MS (ES) 511.17 (M+H), 509.25 (M-H); 1-(2-chloro-7-methylthieno[3,2-£/|pyrimidin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound#60, pale-yellow solid; MS (ES)471.11 (M+H), 469.19 (M-H); 1-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-c(|pyrimidin-4-yl)-H3-(4-(2-(pyrrolidin-1- yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #61, pale-yellow solid; MS (ES) 477.46 (M+H), 475.15 (M-H); A/3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(isoquinolin-1-yl)-1H-1,2,4-triazole-3,5-diamine, compound #62, yellow solid; MS (ES) 450.21 (M+H), 448.02 (M-H); 1-(6-fluoroquinazolin-4-yl)-H3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #63, yellow solid; MS (ES) 435.62 (M+H), 433.21 (M-H); /V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(thieno[2,3-c]pyridin-7-yl)-1H-1,2,4-triazole-3,5-diamine, compound #64, pale-brown solid; MS (ES) 422.48 (M+H), 420.01 (M-H); 1-(2-methylquinazolin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #65, yellow solid; MS (ES) 431.41 (M+H); 1-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-c/]pyrimidin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #66, off-white solid; MS (ES) 463.29 (M+H), 461.20 (M-H); A/3-(3-chioro-4-(2-(pyrroiidin-1-yl)ethoxy)phenyl)-1-(5,6,7)8- tetrahydrobenzo[4,5]thieno[2,3-d] pyrimidin-4-yl)-1W-1,2,4-triazole-3,5-diamine, compound #67, pale-yellow solid; MS (ES) 511.20 (M+H), 509.20 (M-H); A/3-(3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(5,6,7l8- tetrahydrobenzo[4,5]thieno[2,3-cf]pyrimidin-4-yl)-1W-1,2,4-triazole-3,5-diamine, compound #68, yellow solid; MS (ES) 495.26 (M+H), 493.29 (M-H); 1 -(furo[3,2-c]pyridin-4-yl)-/\/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #69, pale-brown solid; MS (ES) 406.47 (M+H); 1-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-of]pyrimidin-4-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #70, yellow solid; MS (ES) 491.24 (M+H), 489.67 (M-H); 1-(benzothieno[3,2-cf]pyrimidin-4-yl)-/\/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #71, orange solid; MS (ES) 473.07 (M+H), 471.44 (M-H); 1 -(5,6-dihydrobenzo[/)]quinazolin-2-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 H-\,2,4-triazole-3,5-diamine, compound #72,1H NMR (DMSO-cfe, 300 MHz) 8.85 (s, 1H), 8.66 (s, 1H), 8.16 (d, 1H), 7.66 (s, 1H), 7.55 (d, 2H), 7.48 (m, 2H), 7.38 (d, 1H), 6.84 (d, 2H), 4.00 (t, 2H), 2.95 (m, 4H), 2.80 (t, 2H), 2.50 (m, 6H), 1.69 (m, 2H) ppm; MS (ES) 469.29 (M+H); 1-(7-fert-butyl-5,6,7l8-tetrahydrobenzo[4,5]thieno[2,3-cf]pyrimidin-4-yl)-/\/3-(4-(2- (pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #73, off-white solid; MS (ES) 533.42 (M+H), 531.39 (M-H); 1-(5,6,6a,7,8,9,10,10a-octahydrobenzo[/7]quinazolin-2-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyi)-1H-1,2,4-triazole-3,5-diamine, compound #74,1H NMR (DMSO-cfe, 300 MHz) 8.55 (s, 1H), 8.45 (s, 1H), 7.52 (d, 2H), 6.81 (d, 2H), 4.00 (t, 2H), 3.13 (m, 4H), 2.76 (t, 2H), 2.49 (m, 4H), 2.39(m, 1H), 1.88-1.60 (m, 7H), 1.55-1.50 (m, 6H) ppm; MS (ES) 475 (M+H); 1 -(5,6-dihydrobenzo[/?]cinnolin-3-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1 W-1,2,4-triazole-3,5-diamine, compound #75,1H NMR (DMSO-cfe, 300 MHz) 8.98 (s, 1H), 8.32 (m, 1H), 7.85 (s, 1H), 7.78 (s, 1H) 7.54 (d, 2H), 7.34-7.40 (m, 3H), 6.87 (d, 2H), 4.07 (t, 2H), 3.08 (m, 2H), 2.95 (m, 2H), 2.75 (m, 2H), 2.49 (m,2H), 1.76 (m, 6H) ppm; MS (ES) 469.30 (M+H); 2-(5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1W-1,2,4-triazol-1-yl)-5,6,7,8-tetrahydroquinazolin-4-ol, compound #76, yellow solid; MS (ES) 437.28 (M+H), 435.27 (M-H); 1-(6,7-dlmethoxyisoquinolin-1-yl)-/V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl )-1 W-1,2,4-triazole-3,5-diamine, compound #77, off-white solid; MS (ES) 476.40 (M+H); 5-(5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1H-1,2,4-triazol-1-yl)-1,6-naphthyridin-2(1 W)-one, compound #78, yellow solid; MS (ES) 433.56 (M+H), 431.24 (M-H); benzyl 3-(5-amino-3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenylamino)-1 H-1,2,4-triazol-1 -yl)-7,8-dihydropyrido[4,3-c]pyridazine-6(5H)-carboxylate, compound #79,1H NMR (CDCI3, 300 MHz) 7.62 (s, 1H), 7.32 (m, 6H), 7.07 (m, 1H), 6.83 (d, 2H), 5.17 (s, 2H), 4.66 (m, 2H), 4.07 (m, 2H), 3.81 (m, 2H), 3.13 (m, 2H), 2.89 (m, 2H), 2.66 (m, 4H), 1.79 (m, 4H) ppm; MS (ES) 556.42 (M+H); A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl )-1-(5,6,7,8-tetrahydropyrido[4,3-c]pyridazin-3-yl)-1H-1,2,4-triazole-3,5-diamine, compound #80,1H NMR (CDCl3/MeOD4, 300 MHz) 8.30 (s, 1H), 7.42 (d, 2H), 6.89 (d, 2H), 4.25 (m, 2H), 3.11-3.16 (m, 12H), 2.01 (m, 4H) ppm; MS (ES) 422.16 (M+H); /V3-(4-(4-cyclohexylpiperazin-1 -yl)phenyl)-1 -(isoquinolin-1 -yl)-1 W-1,2,4-triazole-3,5-diamine, compound #81, yellow solid; MS (ES) 469.56 (M+H); 4-(5-amino-3-(4-(4-cyclohexylpiperazin-1-yl)phenylamino)-1/4-1,2,4-triazol-1-yl )-6- methoxyquinazolin-7-ol, compound #82, yellow solid; MS (ES) 516.52 (M+H), 514.33 (M-H); A/5-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1 -(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4- triazole-3,5-diamine, compound #83, yellow solid; MS (ES) 530.53 (M+H), 528.31 (M-H); 1-(isoquinolin-1-yl)-/V3-(4-(4-methylpiperazin-1-yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine, compound #84, yellow solid; MS (ES) 401.38 (M+H); 1-(6-chloroquinazolin-4-yl)-W3-(4-(4-methylpiperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine, compound #85, yellow solid; MS (ES) 436.04 (M+H), 434.20 (M-H); 1-(6-chloroquinazolin-4-yl)-A/5-(4-(4-methylpiperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #86, yellow solid; MS (ES) 436.08 (M+H); A/3-(4-(4-cyclohexylpiperazln-1-yl)-3-fluorophenyl)-1-(isoquinolin-1-yl )-1/-/-1,2,4-triazole- 3,5-diamine, compound #87, pale-yellow solid; MS (ES) 487.63 (M+H), 485.15 (M-Η); 1-(4-(4-(5-amino-1-(isoquinolin-1-yl)-1H-1,2,4-triazol-3-ylamino)phenyl)piperazin-1- yl)ethanone, compound #88, brown solid; MS (ES) 429.10 (M+H), 426.93 (M-H); A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)plperazin-1-yl)phenyl)-1-(isoquinolin-1-yl)-1H-1,2,4-triazole-3,5-diamine, compound #89, yellow solid; MS (ES) 481.34 (M+H), 479.06 (M-H); /V3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(isoquinolln-1-yl)-1W-1,2,4-triazole-3,5-diamine, compound #90, yellow solid; MS (ES) 419,37 (M+H), 417.20 (M-H); A/3-(3-chloro-4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(isoquinolin-1-yl)-1H-1,2,4-triazole- 3,5-diamine, compound #91, pale-brown solid; MS (ES) 503,26 (M+H), 501.58 (M-H); A/3-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(5,6-dihydrobenzo[/7]quinazolin-2-yl)-1/-/- 1.2.4- triazole-3,5-diamine, compound #93,1H NMR (DMSO-Gf6, 300 MHz) 8.76 (s, 1H), 8.65 (s, 1H), 8.16 (d, 1H), 7.65 (s, 2H), 7.48 (Μ, 4H), 7.38 (d, 1H), 6.84 (d, 2H), 2.95 (m, 8H), 2.61 (m, 4H), 1.72 (Μ, 4H), 1.57 (m, 1H), 1.20-1.01 (m, 6H) ppm; MS (ES) 522.38 (M+H); A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(pyridin-2-yl)-1/-/-1,2,4- triazole-3,5-diamine, compound #94, pale-brown solid; MS (ES) 431.20 (M+H); 1-(benzo[c/|thiazol-2-yl)-/Vs-(4-(4-(blcyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H- 1.2.4- triazole-3,5-diamine, compound #95, off-white solid; MS (ES) 487.27 (M+H), 485.25 (M-H); 1-(benzo[c/jthiazol-2-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H- 1.2.4- triazole-3,5-diamine, compound #96, off-white solid; MS (ES) 487.24 (M+H), 485.20 (M-H); W3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1-yl)phenyl)-1-(quinoxalin-2-yl)-1 W-1,2,4-triazole-3,5-diamine, compound #97, orange solid; MS (ES) 482.52 (M+H), 480.18 (M-H); A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1W-1,2,4-triazole-3,5-diamine, compound #98, pale-yellow solid; MS (ES) 542.30 (M+H), 540.59 (M-H); A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-chloro-7-methylthieno[3,2-cdpyrimidin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #99, yellow solid; MS (ES) 536.18 (M+H), 535.51 (M-H); W5-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1/-/-1,2,4-triazole-3,5-diamine, compound #100, yellow solid; MS (ES) 542.47 (M+H), 540.22 (M-H); A/3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1-(2-chloro-6,7- dimethoxyquinazolin-4-yl )-1 H-1,2,4-triazole-3,5-diamine, compound #101, yellow solid; MS (ES) 576.19 (M+H), 574.22 (M-H); 4-(5-amino-3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenylamino)-1H-1,2,4- triazol-1-yl)-2-chloro-6-methoxyquinazorm-7-ol, compound #102, yellow solid; MS (ES) 562.21 (M+H), 560.33 (M-H); A/3-(4-(4-(blcyclo(2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6-chloroquinazolin-4-yl)-1H- 1.2.4- triazole-3,5-diamine, compound #103, yellow solid; MS (ES) 516.21 (M+H), 514.26 (M-H); 1 -(7-(benzyloxy)-6-methoxyquinazolin-4-yl)-A/3-(4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl)-1 H- 1.2.4- triazole-3,5-diamine, compound #104, yellow solid; MS (ES) 553.45 (M+H), 551.33 (M-H); 1-(6,7-dimethoxyquinazolin-4-yl)-/V3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #105, yellow solid; MS (ES) 480.84 (M+H); 4-(5-amino-3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)-3-fluorophenylamino)-1H- 1.2.4- triazol-1-yl)-6-methoxyquinazolin-7-ol, compound #106, yellow solid; MS (ES) 546.22 (M+H), 544.33 (M-H); 1-(4-(4-(5-amino-1-(6,7-dimethoxyquinazolln-4-yl)-lH-1,2,4-triazol-3- ylamino)phenyl)piperazin-1-yl)ethanone, compound #107, yellow solid; MS (ES) 490.32 (M+H); 1 -(5,6-dihydrobenzo[/7]cinnolin-3-yl)-/\/3-(4-(4-methylpiperazin-1-yl)phenyl)-1 W-1,2,4- triazole-3,5-diamine, compound #108,1H NMR (CDCI3/MeOD4l 300 MHz) 7.65 (s, 1H), 7.33 (d, 1H), 7.27 (d, 2H), 7.15-7.25 (m, 2H), 7.08 (m, 1H), 6.77 (d, 2H), 2.81-2.98 (m, 8H), 2.45 (Μ, 4H), 2.17 (s, 3H) ppm; MS (ES) 454.30 (M+H); 4-(5-amino-3-(4-(4-cycloheptylpiperazin-1 -yl)phenylamino)-1 H-1,2,4-triazol-1 -yl)-6-methoxyquinazolin-7-ol, compound #109, yellow solid; MS (ES) 530.22 (M+H), 528.01 (M-H); A/3-(4-(4-cycloheptylpiperazin-1-yl)phenyl )-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #110, yellow solid; MS (ES) 544.30 (M+H); A/3-(4-(4-adamantan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxy-quinazolin-4-yl)-1H- 1.2.4- triazole-3,5-diamine, compound #111, yellow solid; MS (ES) 582.48 (M+H); /V3-(4-(4-cydooctylpiperazin-1-yl)phenyl)-1 -(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4- triazole-3,5-diamine, compound #112, yellow solid; MS (ES) 558.25 (M+H), 556.39 (M-H); 5-(5-amino-3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)-1H-1,2,4-triazol-1-yl)-1,6-naphthyridin-2(1H)-one, compound #113, dark-yallow solid; MS (ES) 436,20 (M+H), 434.20 (M-H); W3-(3-chloro-4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1H- 1.2.4- triazole-3,5-diamine, compound #114, yellow solid; MS (ES) 564.21 (M+H); A/3-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(5,6-dihydrobenzo[/?]cinnolin-3-yl)-1H-1,2,4- triazole-3,5-diamine, compound #115,1H NMR (CDCI3/MeOD4, 300 MHz) 8.22 (s, 1H), 7.66 (s, 1H), 7.52 (d, 2H), 7.34 (m, 2H), 7.28 (m, 2H), 6.89 (d, 2H), 3.29 (m, 4H), 2.91-3.05 (m, 7H), 2.81 (m, 1H), 2.00 (m, 2H), 1.85 (m, 2H), 1.63 (m, 1H), 1.07-1.40 (m, 5H) ppm; MS (ES) 522.24 (M+H); 4-(5-amino-3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)-1H-1,2,4-triazoM- yl)quinazoline-6,7-diol, compound #116, off-white solid; MS (ES) 452.23 (M+H), 450.18 (M-H); 4- (5-amino-3-(3-fluoro-4-(4-methylpiperazin-1 -yl)phenylamino)-1 H-1,2,4-triazol-1 -yl)-6- methoxyquinazolin-7-ol, compound #117, pale-yellow solid; MS (ES) 466.41 (M+H), 464.25 (M-H); A/3-(4-(4-(bicyclo[3.3.1]nonan-9-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1 H-1,2,4-triazole-3,5-diamine, compound #118, yellow solid; MS (ES) 570.27 (M+H), 568.38 (M-H); /^-( 4-chloro-3-( 4-ethyl piperazin-1 -yl)phenyl)-1 -(6,7-dimethoxyquinazolin-4-yl)-1 H-1,2,4-triazole-3,5-diamine, compound #119, yellow solid; MS (ES) 511.75 (M+H), 508.25 (M-H); 1-(4-(5-( 5-amino-1-(6,7-dimethoxyquinazolin-4-yl)-1 H-1,2,4-triazol-3-ylamino)-2- chlorophenyl)piperazin-1-yl)ethanone, compound #120, yellow solid; MS (ES) 524.16 (M+H), 522.24 (M-H); 5- (5-amino-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazol-3-ylamino)-2-(4- methylpiperazin-1-yl)benzamide, compound #121, yellow solid; MS (ES) 505.27 (M+H), 503.23 (M-H); A/3-(4-(4-cyclohexylpiperazln-1-yl)-3-fluorophenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1/-/- 1.2.4- triazole-3,5-diamine, compound #122, yellow solid; MS (ES) 548.53 (M+H), 546.33 (M-H); /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)-3-fluorophenyl)-1-(6,7- dimethoxyquinazolin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #123, yellow solid; MS (ES) 560.35 (M+H), 558.34 (M-H); /V3-(4-(4-(bicyclo[3.2.0)heptan-6-yl)piperazin-1-yl)phenyl )-1-(6,7-dimethoxyquinazolin-4- yl)-1H-1,2,4-triazole-3,5-diamine, compound #124, yellow solid; MS (ES) 542.54 (M+H), 540.32 (M-H); A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dimethoxyisoquinolin-1-yl)-1H-1,2,4-triazole-3,5-diamine, compound #125, pale-yellow solid; MS (ES) 541.38 (M+H); W3-(4-(4-cycloheptylpiperazin-1-yl)phenyl )-1-(6,7-dimethoxyisoquinolin-1-yl)-1W-1,2,4-triazole-3,5-diamine, compound #126, pale-yellow solid; MS (ES) 543.63 (M+H); A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(thieno[2,3-c/]pyrimidin-4-yl)-1W-1,2,4-triazole-3,5-diamine, compound #127, yellow solid; MS (ES) 488.77 (M+H), 486.27 (M-H); /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(thieno[3,2-c/]pyrimidin-4-yl)-1W-1,2,4-triazole-3,5-diamine, compound #128, pale-yellow solid; MS (ES) 488.69 (M+H), 486.29 (M-H); /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6-phenylthieno[3,2- c/]pyrimidin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #129, yellow solid; MS (ES) 564.71 (M+H), 562.37 (M-H); /V3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-2-(6-phenylthieno[2,3- c/]pyrimidin-4-yl)-2tf-1,2,4-triazole-3,5-diamine, compound #130, yellow solid; MS (ES) 564.69 (M+H), 562.37 (M-H); /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(furo[3,2-c]pyridin-4-yl )-1/-/- 1.2.4- triazole-3,5-diamine, compound #131, off-white solid; MS (ES) 471.62 (M+H), 469.39 (M-H); /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6,7-dihydro-5/+ cyclopenta [4,5]thieno[2,3-cf]pyrimidin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #132, yellow solid; MS (ES) 528.82 (M+H), 526.35 (M-H); A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(6-fluoroquinazolin-4-yl)-1H- 1.2.4- triazole-3,5-diamine, compound #133, orange solid; MS (ES) 500.71 (M+H), 498.34 (M-H); A/3-(4-(1-(bicyclo[2.2.1]heptan-2-yl)piperidin-4-yl)phenyl)-1-(2-chloro-7-methylthieno[3,2-c(]pyrimidin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #134, pale-yellow solid; MS (ES) 535.27 (M+H), 533.31 (M-H); W3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-methylquinazolin-4-yl)-1H-1,2,4~triazole-3,5-diamine, compound #135, red solid; MS (ES) 496.64 (M+H), 494.38 (M-H); W3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-(trifluoromethyl)quinazolin- 4-yl)-1/7-1,2,4-triazole-3,5-diamine, compound #136, orange solid; MS (ES) 550.75 (M+H), 548.39 (M-H); A/3-(4-(4-(bicyclo[2,2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2,5,6-trimethylthieno[2,3- c/|pyrimidin-4-yl)-1/7-1,2,4-triazole-3,5-diamine, compound #137, yellow solid; MS (ES) 530.59 (M+H), 528.40 (M-H); /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(5,6-dimethylthieno[2,3- c/|pyrimidin-4-yl)-1W-1,2,4-triazole-3,5-diamine, compound #138, yellow solid; MS (ES) 516.74 (M+H), 514.36 (M-H); A/3-(4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)-3-fluorophenyl)-1 -(2-chloro-7- methylthieno[3,2-c/)pyrimidin-4-yl)-1/7-1,2,4-triazole-3,5-diamine, compound #140, pale-yellow solid; MS (ES) 554.20 (M+H), 552.30 (M-H); /V3-(4-(4-((1R,2R,4S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(2-chloro-7- methylthieno[3,2-c/)pyrimidin-4-yl)-1 /7-1,2,4-triazole-3,5-diamine, compound #141, yellow solid; MS (ES) 536.19 (M+H), 534.16 (M-H); /V3-(4-methoxyphenyl)-1 -(pyridin-2-yl)-1/7-1,2,4-triazde-3,5-diamine, compound #142, tan solid; MS (ES) 283.46 (M+H); ethyl 4-(5-amino-1-(2-chloropyridin-4-yl)-1/7-1,2,4-triazol-3-ylamino)benzoate, compound #143, pale-yellow solid; MS (ES) 359.02 (M+H), 357.02 (M-H); 1-(4-(5-amino-1-(quinoxalin-2-yl )-1/-/-1,2,4-triazol-3-ylamino)phenyl)ethanone, compound #144, tan solid; MS (ES) 346.00 (M+H), 344.19 (M-H); (SJ-ethyl 4-(5-amino-1-(2-(2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)pyridin-4-yl)-1/7-1,2,4-triazol-3-ylamino)benzoate, compound #145, pale-brown solid; MS (ES) 477.19 (M+H), 475.27 (M-H); (S>4-(5-amino-1-(2-(2-(pyrrolidln-1-ylmethyl)pyrrolidin-1-yl)pyridin-4-yl)-1/7-1,2,4-triazol- 3-ylamino)benzoic acid, compound #146, brown solid; MS (ES) 449.17 (M+H), 447.23 (M-H); 1 -(4-(5-amino-1 -(2-fluorophenyl)-1 /7-1,2,4-triazol-3-ylamino)phenyl)ethanone, compound #147, pale-yellow solid; MS (ES) 312.33 (M+H), 310.11 (M-H); 1 -(pyridin^-yO-A/^SAe-trimethoxyphenyO-l /7-1,2,4-triazole-3,5-diamine, compound #148, off-white solid; MS (ES) 343.60 (M+H), 341.14 (M-H); 1-(pyridin-2-yl)-/V3-(3,4,5-trifluorophenyl)-1/7-1,2,4-triazole-3,5-diamine, compound #149, off-white solid; MS (ES) 307.14 (M+H), 305.03 (M-H); 3-(5-amino-1-(pyridin-2-yl)-1/7-1,2,4-triazol-3-ylamino)phenol, compound #150, off-white solid; MS (ES) 269.54 (M+H), 267.08 (M-H); /V®.(4-((1 .methylpyrrolidin-2-yl)methoxy)phenyl)-1-(quinoxalin-2-yl)-1/7-1,2,4-triazole-3,5-diamine, compound #151, yellow solid; MS (ES) 417.62 (M+H), 415.23 (M-H); 3-(4-(5-amino-1-(quinoxalin-2-yl)-1H-1,2,4-triazol-3-ylamino)phenyl)-1-(pyrrolidin-1-yl)propan-1-one, compound #152, MS (ES) 429.57 (M+H), 427.50 (M-H); 1-(6,7-dimethoxyquinazolin-4-yl)-/\/3-(4-(1-methylpiperidin-3-yloxy)phenyl )-1 W-1,2,4-triazole-3,5-diamine, compound #153, yellow solid; MS (ES) 477.60 (M+H), 475.15 (M-H); 1-(6,7-dimethoxyquinazolin-4-yl)-/\/5-(4-(1-methylpiperidin-3-yloxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #154, yellow solid; MS (ES) 477.43 (M+H), 475.25 (M-H); 1 -(isoquinolin-1 -yl)-A/3-(4-(1-methylpiperidin-3-yloxy)phenyl)-1 H-1,2,4-triazole-3,5- diamine, compound #155, off-white solid; MS (ES) 416.44 (M+H), 414.16 (M-H); 1-(isoquinolin-1-yl)-A/3-(4-morpholinophenyl)-1 HA,2,4-triazole-3,5-diamine, compound #156, yellow solid; MS (ES) 388.39 (M+H); 1 -(isoquinolin-1 -yO-A^-^morpholinophenylJ-l/-/-1,2,4-triazole-3,5-diamine, compound #157, yellow solid; MS (ES) 388.60 (M+H), 386.16 (M-H); 1-(6,7-dimethoxyquinazolin-4-yl)-W3-(4-morpholinophenyl)-1W-1,2,4-triazole-3,5-diamine, compound #158, yellow solid; MS (ES) 449.30 (M+H), 447.02 (M-H); /^-(S-chlorcM-morpholinophenyO-l -(6,7-dimethoxyquinazolin-4-yl)-1 H-1,2,4-triazole-3,5-diamine, compound #159, yellow solid; MS (ES) 483.08 (M+H), 481.00 (M-H); /^-(S-chlortMt-morpholinophenylH -(6-chloroqumazolin-4-yl)-1 H-1,2,4-tri azol e-3,5-diamine, compound #160, off-white solid; MS (ES) 458.08 (M+H); A/3-(3-fluoro-4-morpholinophenyl)-1-(isoquinolin-1-yl)-1H-1,2,4-triazole-3,5-diamine, compound #161, yellow solid; MS (ES) 406.49 (M+H), 404.16 (M-H); 1-(6,7-dimethoxyquinazolin-4-yl)-W3-(3-fluoro-4-morpholinophenyl)-1/-/-1,2,4-triazole-3,5-diamine, compound #162, yellow solid; MS (ES) 467,13 (M+H); 1-(isoquinolin-1-yl)-A/3-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #163, yellow solid; MS (ES) 415.14 (M+H); /V3-(4-((R)-3-(dimethylamino)pyrrolidin-1-yl)phenyl )-1-(isoquinolin-1-yl )-1/-/-1,2,4-triazole- 3.5- diamine, compound #164, yellow solid; MS (ES) 415.23 (M+H); /^-( 4-((S)-3-(dimethylamino)pyrrolidin-1-yl)phenyl)-1-(isoquinolin-1-yl )-1//-1,2,4-triazole- 3.5- diamine, compound #165, yellow solid; MS (ES) 415.12 (M+H); 1-(isoquinolin-1-yl)-A/3-(4-(oxazol-5-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #166, yellow solid; MS (ES) 370.49 (M+H), 368.15 (M-H); 1-(isoquinoiin-1-yl)-A/3-(4-(1-methylpiperidin-4-yl)phenyl)-1/+1,2,4-triazoIe-3,5-diamine, compound #167, pale-yellow solid; MS (ES) 400.38 (M+H); 1-(6,7-dimethoxyquinazolin-4-yl)-A/3-(4-(1-methylpiperidin-4-yl)phenyl)-1/V-1,2,4-triazole- 3.5- diamine, compound #168, yellow solid; MS (ES) 461.61 (M+H), 459.28 (M-H); 4-(5-amino-3-(4-(1-methylpiperidin-4-yl)phenylamino)-1/-/-1,2,4-triazol-1-yl)-6- methoxyquinazolin-7-ol, compound #169, pale-yellow solid; MS (ES) 446.92 (M+H), 445.25 (M-H); 1-(6,7-dimethoxyquinazolin-4-yl)-/V3-(4-((S)-3-(dimethylamino)pyrrolidin-1-yl)phenyl)-1H- 1.2.4- triazole-3,5-diamine, compound #171, yellow solid; MS (ES) 476.35 (M+H); 4-(5-amino-3-(4-(1-methylpiperidin-4-yl)phenylamino)-1H-1,2,4-triazol-1-yl)quinazoline- 6,7-diol, compound #172, pale-yellow solid; MS (ES) 433.07 (M+H), 431.54 (ΜΗ); 1 -(6,7-dimethoxyquinazolin-4-yl)-/V3-(4-((4-methylpiperazin-1 -yl)methyl)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #173, yellow solid; MS (ES) 476.09 (M+H), 474.26 (M-H); 1 -(6,7-dlmethoxyisoquinolin-1 -yl)-N®-(4-(1 -methylpiperidin-4-yl)phenyl)-1 H-1,2,4-triazole- 3.5- diamine, compound #174, pale-yellow solid; MS(ES) 460.44 (M+H); 1 -(2,6-dichlorothieno[3,2-c/lpyrimidin-4-yl)-/\/3-(4-(2-pyrrolidin-1 -ylethoxy)phenyl)-1 H- 1.2.4- triazole-3,5-diamine, compound #175,1H NMR (DMSO-de, 300 MHz) 9.36 (s, 1H), 8.63 (s, 1H), 8.17 (s, 1H), 7.96 (brs, 2H), 7.58 (d, 2H), 6.93 (d, 2H), 6.55 (s, 1H), 4.04 (t, 2H), 2.79 (m, 2H), 1.70 (m, 4H), 1.04 (m, 4H) ppm; MS (ES) 491.03 (M+); 1-(2-chlorothieno[2,3-£/|pyrimidin-4-yl)-/\/3-(4-(2-pyrrolidin-1-ylethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #176,1H NMR (DMSO-d6, 300 MHz) 9.21 (s, 1H), 8.32 (d, 1H), 7.99 (br s, 2H), 7.91 (d, 1H), 7.49 (d, 2H), 6.93 (d, 2H), 4.06 (t, 2H), 2.89 (m, 2H), 2.65 (m, 4H), 1.73 (m, 4H) ppm; MS (ES) 457.07 (M+); 1 -(2-chlorothleno[3,2-c/|pyrimidin-4-yl)-/V3-(4-(2-pyrrolidin-1-ylethoxy)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine, compound #177,1H NMR (DMSO-d6, 300 MHz) 9.28 (s, 1H), 8.55 (d, 1H), 8.17 (s, 1H), 7.92 (brs, 2H), 7.58 (m, 3H), 6.92 (d, 2H), 4.02 (t, 2H), 2.76 (m, 2H), 2.40 (m, 4H), 1.67 (m, 4H) ppm; MS (ES) 457.01 (M+); /V3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(6,7,8,9-tetrahydro-5H- cyclohepta[4,5]thieno[2,3-c/|pyrimidin-4-yl)-1H-1,2,4-triazole-3,5-diamine, compound #178, pale-yellow solid. MS (ES) 491.24 (M+H), 489.61 (M-H); 1-(2-chlorothieno[3,2-c/|pyrimidin-4-yl)-/V3-(4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #179,1H NMR (DMSO-d6, 300 MHz) 9.21 (s, 1H), 8.55 (d, 1H), 7.91 (br s, 2H), 7.58 (m, 3H), 6.92 (d, 2H), 3.05 (m, 5H), 2.72 (s, 1H), 2.43 (m, 4H), 2.30 (m, 2H), 2.18 (t, 1H), 1.40 (m, 2H), 1.22 (m, 4H) ppm; MS (ES) 522.04 (M+); 1-(6,7-dimethoxyquinazolin-2-yl)-A/3-(4-(4-methylpiperazin-1-yl)phenyl)-1/-/-1,2,4-triazole- 3,5-diamine, compound #180,1H-NMR (CDCI3, 300 MHz) 9.36 (s, 1H), 7.50 (d, 2H), 7.40 (s, 1H), 7.18 (s, 1H), 6.95 (d, 2H), 6.80 (s, 2H), 6.62 (s, 1H), 4.02 (s, 6H), 3.19 (m, 4H), 2.60 (m, 4H), 2.35 (s, 3H) ppm; MS (ES) 462 (M+H); 1-(6,7-dimethoxyquinazolin-2-yl)-/V3-(3-fluoro-4-(4-cyclohexylpiperazin-1-yl)phenyl)-1 H- 1,2,4-triazole-3,5-diamine, compound #181,1H-NMR(CDCI3l 300 MHz) 9.31 (s, 1H), 7.47 (m, 1H), 7.40 (s, 1H), 7.16 (s, 1H), 7.13 (m, 1H), 6.96 (t, 1H), 6.77 (s, 2H), 6.70 (s, 1H), 4.07 (s, 6H), 3.08 (m, 2H), 2.79 (m, 2H), 2.35 (m, 1H), 1.96 (m, 2H), 1.83 (m, 2H), 1.67 (m, 4H), 1.26 (m, 2H) ppm; MS (ES) 548 (M+H); 1-(6,7-dimethoxyquinazolin-2-yl)-A/3-(4-(4-((1S,2S,4/?)-bicyclo[2.2.1]heptan-2-yl)- piperazin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine (racemic), compound #182, 1H-NMR (CDCI3, 300 MHz) 9.10 (s, 1H), 7.36 (d, 2H), 7.22 (s, 1H), 7.08 (s, 1H), 6.85 (d, 2H), 3.93 (m, 10H), 3.02 (m, 3H), 2.48 (m, 3H), 2.21 (m, 1H), 2.07 (m, 1H), 1.61 (m, 2H), 1.40 (m, 1H), 1.19 (m, 3H), 0.80 (m, 1H) ppm; MS (ES) 542.38 (M+H); 1-(7-methyl-2-chlorothieno[3,2-c/]pyrimidin-4-yl)-A/3-(4-(4-((1S,2S,4/?)- bicyclo[2.2.1 ]heptan-2-yl)-plperazin-1-yl)phenyl )-1 W-1,2,4-triazole-3,5-diamine (racemic), compound #183,1H-NMR (DMSO-d6l 300 MHz) 9.17 (s, 1H), 8.18 (s, 1H), 7.89 (broad s, 2H), 7.55 (d, 2H), 6.91 (d, 2H), 3.28 (m, 2H), 3.05 (m, 3H), 2.48 (m, 3H), 2.36 (s, 3H), 2.10-2.29 (m, 3H), 1.90 (m, 1H), 1.71 (m, 2H), 1.45 (m, 1H), 1.20-1.40 (m, 3H), 0.87 (m, 1H) ppm; MS (ES) 536.10 (M+H); 1-(pyrido[2,3-b]pyrimido[4,5-d]thlophene-4-yl)-A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)- piperazin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #184,1H NMR (DMSO-dg, 300 MHz) 9.15 (brs, 1H), 9.02 (s, 1H), 8.92 (d, 1H), 8.77 (d, 1H), 8.10 (br s, 2H), 7.70 (dd, 1H), 7.59 (d, 2H), 6.93 (d, 2H), 3.08 (m, 4H), 2.48 (m, 4H), 2.30-2.14(m, 3H), 1.80-1.62 (m, 2H), 1.46-1.15(m, 5H), 0.90-0.86 (m, 1H) ppm; MS (ES) 539.67 (M+H); 1-(5-(thiophen-2-yl)thieno[2,3-d]pyrimidin-4-yl)-/\/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #185,1H NMR (DMSO-de, 300 MHz) 8.93 (br s. 1H), 8.32 (s, 1H), 8.03 (s, 1H), 7.30 (d, 1H), 7.02 (br s, 2H), 6.97 (m, 1H), 6.93 (d, 2H), 6.78-6.76 (m, 1H), 6.67 (d, 2H), 2.96 (m, 4H), 2.42 (m, 4H), 2.28-2.13 (m, 3H), 1.70-1.60 (m, 2H), 1.45-1.14 (m, 5H), 0.90-0.80 (m, 1H) ppm; MS (ES) 570.38 (M+H); 1-(6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-(blcyclo[2.2.1]heptan-2-yl)- piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #186,1H NMR (DMSO-d6, 300 MHz) 9.10 (br s, 1H), 8.81 (s, 1H), 8.05 (br s, 2H), 7.95 (d, 2H), 7.64 (d, 2H), 7.57 (d, 2H), 6.93 (d, 2H), 3.08 (m, 4H), 2,43 (m, 4H), 3.31-2.15 (m, 3H), 1.70-1.63 (m, 2H), 1.46-1.15 (m, 5H), 0.91-0.87 (m, 1H) ppm; MS (ES) 598.16 (M+H); 1-(6-(1,1-dimethylethyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl )-piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #187,1H NMR (DMSO-de, 300 MHz) 9.06 (br s, 1H), 8.76 (s, 1H), 7.99 (br s, 2H), 7.58 (d, 2H), 7.38 (s, 1H), 6.86 (d, 2H), 3.03 (m, 4H), 2.48 (m, 4H), 2,29-2.14 (m,3H), 1.80- 1.64 (m, 2H), 1.49 (s, 6H), 1.48 (s, 3H), 1.32-1.15 (m, 5H), 0.90-0.80 (m, 1H) ppm; MS (ES) 544.81 (M+H); 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-A/3-(4-(4-((1S,2S,4f?)-bicyclo[2.2.1]heptan-2-yl)-piperazin-1 -yl)phenyl)-1 W-1,2,4-triazole-3,5-diamine, compound #188,1H NMR (DMSO-d6, 300 MHz) 9.08 (br s, 1H), 8.85 (s, 1H), 8.12 (s, 1H), 8.06 (br s, 2H), 7.58 (d, 2H), 6.91 (d, 2H), 3.05 (m, 4H), 2.46-2.44 (m, 4H), 2.42 (s, 3H), 2.30-2.14 (m, 3H), 1.80-1.62 (m, 2H), 1.46-1.14 (m, 5H), 0.89-0.86 (m, 1H)ppm; MS (ES) 502.71 (M+H); 1-(thieno[3,2-£/]pyrimidin-4-yl)-/\/3-(4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #189,1H NMR (DMSO-d6, 300 MHz) 9.10 (br s, 1H), 8.82 (s, 1H), 8.47 (d, 1H), 8.06 (br s, 2H), 7.59 (s, 1H), 7.57 (d, 2H), 6.91 (d, 2H), 3.05 (m, 4H), 2.47 (m, 4H), 2,30-2.14 (m, 3H), 1.80- 1.62 (m, 2H), 1.46-1.14 (m, 5H), 0.90-0.86 (m, 1H) ppm; MS (ES) 488.55 (M+H); 1-(thieno[2,3-d]pyrimidin-4-yl)-/V3-(4-(4-((1S,2S,4fi)-bicyclo[2.2.1]heptan-2-yl)-piperazln- 1 -yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine, compound #190,1H NMR (DMSO-de, 300 MHz) 9.02 (br s, 1H), 8.77 (s, 1H), 8.37 (d, 1H), 8.15 (br s, 2H), 7.91 (d, 1H), 7.45 (d, 2H), 6.91 (d, 2H), 3.04 (m, 4H), 2.47 (m, 4H), 2.30-2,14 (m, 3H), 1.80- 1.62 (m, 2H), 1.45-1.14 (m, 5H), 0.89-0.86 (m, 1H) ppm; MS (ES) 488.53 (M+H); 1-(5-methylthieno[2,3-c/]pyrimidin-4-yl)-A/3-(4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)- piperazin-1 -yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine, compound #191,1H NMR (DMSO-d6, 300 MHz) 8.89 (s, 1H), 8.72 (br s, 1H), 7.63 (s, 1H), 7.36 (d, 2H), 7.01 (br s, 2H), 6.79 (d, 2H), 2.98 (m, 4H), 2.42 (m, 4H), 2.30-2.14 (m, 3H), 1.80-1.62 (m, 2H), 1.46-1.14 (m, 5H), 1.24 (s, 3H), 0.90-0.86 (m, 1H) ppm; MS (ES) 502.36 (M+H); 1-(phenanthridin-6-yl)-/V3-(3-fluoro-4-(4-cyclopentylpiperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #192,1H NMR (DMSO-de, 300 MHz) 9.26 (d, 1H), 9.16 (brs, 1H), 9.91 (d, 1H), 8.78 (d, 1H), 8.09 (d, 1H), 7.99 (t, 1H), 7.82- 7.69 (m, 3H), 7.50 (d, 1H). 7.44 (br s, 2H), 7.18 (d, 1H), 6.92 (t, 1H), 2.89 (m, 4H), 2.46 (m, 4H), 2.26 (m, 1H), 1.78 (m, 2H), 1.61-1.51 (m, 4H), 1.36 (m, 2H) ppm; MS (ES) 523.40 (M+H); 1 -(7-methyl-2-chlorothieno[3,2-d]pyrimidin-4-y!)-/\/3-(4-(4-(( 1 S,2S,4R)- blcyclo[2.2,1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-l,2,4-triazole-3,5-diamine, compound #193,1H NMR(DMSO-d6, 300 MHz) 9.30 (brs, 1H), 8.20 (d, 1H), 7.92 (brs, 2H), 7.62 (d, 2H), 7.56 (dd, 2H), 7.30-7.26 (m, 3H), 7.01 (d, 2H), 3.70-3.66 (m, 2H), 3.54-3.46 (m, 2H), 3.26-3.00 (m, 4H), 2.60 (m, 1H), 2.38 (s, 3H), 2.30 (m, 1H), 2.02-1.98 (m, 1H), 1.58 (m, 4H), 1.41 (m, 2H), 1.38 (m, 1H), 1,21-1.16 (m, 1H) ppm; MS (ES) 538.40 (M+H); 1-(7-methylthieno[3,2-c/|pyrimidin-4-yl)-/y3-(3-fluoro-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #194,1H NMR (DMSO-de, 300 MHz) 9.38 (br s, 1H), 8.67 (s, 1H), 8.16 (s, 1H), 8,11 (br s, 2H), 7.63 (d, 1H), 7.32 (d, 1H), 6.99 (t, 1H), 2.95 (m, 4H), 2.56 (m, 4H), 2.42 (s, 3H), 2.85-2.14 (m, 3H), 1.80-1.62 (m, 2H), 1.46-1.14 (m, 5H), 0.88-0.84 (m, 1H) ppm; MS (ES) 520.21 (M+H); 1-(thieno[3>2-c/]pyrimidin-4-yl)-/V3-(3-fluoro-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #195; 1H-NMR (DMSO-d6, 300 MHz) 9.40 (br. s, 1H), 8.84 (s, 1H), 8.52 (d, J = 5.4 Hz, 1H), 8.11 (br. s, 2H), 7.60 (d, J= 5.7 Hz, 1H), 7.33 (d, J= 9.0 Hz, 1H), 7.00 (t, J= 9.9 Hz, 1H), 2.95 (m, 4H), 2.45 (m, 4H), 2.28-2.26 (m, 2H), 2.16-2.14 (m, 1H), 1.73-1.69 (m, 2H), 1.45-1.17 (m, 5H), 0.88-0.85 (m, 1H) ppm; MS (ES) 506.21 (M+H) 1 -(thieno[2,3-cQpyrimidin-4-yl)-A/3-(3-fluoro-4-(4-(bicyclo[2.2.1 ]heptan-2-yl)-piperazin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #196; 1H-NMR (DMSO-d6l 300 MHz) 9.34 (br. s, 1H), 8.79 (s, 1H), 8.33 (d, J = 6.0 Hz, 1H), 8.19 (br. s, 2H), 7.94 (d, »/ = 6.0 Hz, 1H), 7.46 (dd, J= 15.0, 2.4 Hz, 1H), 7.24 (d, J= 9.0 Hz, 1H), 7.00 (t, J= 10.2 Hz, 1H), 2.95 (m, 4H), 2.45 (m, 4H), 2.28-2.25 (m, 2H), 2.16-2.14 (m, 1H), 1.72-1.64 (m, 2H), 1.45-1.17 (m, 5H), 0.88-0.84 (m, 1H) ppm; MS (ES) 506.20 (M+H); 1-(6-fluoroquinazolin-4-yl )-/^-( 3-fluoro-4-(4-(bicyclo|2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine, compound #197; 1H-NMR (DMSO-d6, 300 MHz) 9.50 (dd, J- 11.1, 3.0 Hz, 1H), 9.42 (br. s, 1H), 8.93(s, 1H), 8.35 (br. s, 2H), 8.07-8.02 (m, 1H), 7.98-7.91 (m, 1H), 7.54 (dd, J= 15.3, 2.4 Hz, 1H), 7.18 (d, J= 8.1 Hz, 1H), 6.97 (t, J = 6.0 Hz, 1H), 2.94 (m, 4H), 2.42 (m, 4H), 2.28-2.25 (m, 2H), 2.16-2.14 (m, 1H), 1.72-1.60 (m, 2H), 1.45-1.16 (m, 5H), 0.88-0.84 (m, 1H) ppm; MS (ES) 518.24 (M+H); 1 -(4-methylthieno[3,2-c/]pyrida2in-7-yl)-A/3-(4-(4-(bicydo[2.2.1]heptan-2-yl)-piperazin-1 -yl)phenyl)-1/7-1,2,4-triazole-3,5-diamine, compound #198; 1 -(7-methylthieno[3,2-c/]pyrimidin-4-yl)-A/3-(3-methyl-4-(4-(bicydo[2.2.1 ]heptan-2-yl)-piperazin-1 -yl)phenyl)-1 /7-1,2,4-triazole-3,5-diamine, compound #199; 1 -(7-methyl-2-chlorothieno[3,2-d]pyrimidin-4-yl)-W3-(2-methyl-4-(4-(bicyclo[2.2.1 Jheptan-2-yl)-piperazin-1-yl)phenyl)-1 /7-1,2,4-triazole-3,5-diamine, compound #200; 1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-W3-(3-fluoro-4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/7-1,2,4-triazole-3,5-diamine (TFA salt), compound #201; 1-(7-methylthieno[3,2-c(lpyrimidin-4-yl)-A/3-(2-methyl-4-(4-(bicyclo[2.2.1]heptan-2-yl)- piperazin-1-yl)phenyl)-1/7-1,2,4-triazole-3,5-diamine (TFA salt), compound #202; 1-(4-methylthieno[3,2-d]pyridazin-7-yl)-/\/3-(3-fIuoro-4-(4-(bicyclo[2.2.1]heptan-2-yl)- piperazin-1-yl)phenyl)-1/7-1,2,4-triazole-3,5-diamine (TFA salt), compound #203; 1-(6-(1,1-dimethylethyl)thieno[3,2-d]pyrimidln-4-yl)-/V5-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/7-1,2,4-triazole-3,5-diamine, compound #204,1H NMR (DMSO-d6, 300 MHz) 10.89 (br s, 1H), 8.85 (s, 1H), 7.60 (d, 2H), 7.36 (s, 1H), 7.93 (d, 2H), 6.09 (br s, 2H), 3.09 (m, 4H), 2.47 (m, 4H), 2.29-2.14 (m, 3H), 1.80- 1.60 (m, 2H), 1.45 (s, 6H), 1.44 (s, 3H), 1.42-1.16 (m, 5H), 0.89-0.85 (m, 1H) ppm; MS (ES) 544.81 (M+H); 1-(phenanthridin-6-yl)-/V5-(3-fluoro-4-(4-cyclopentylpiperazin-1-yl)phenyl)-1/7-1,2,4- triazole-3,5-diamine, compound #205,1H NMR (DMSO-de, 300 MHz) 10.49 (br s, 1H), 9.27-9.25 (m, 1H), 9.17 (m, 1H), 8.91-8.89 (m, 1H), 8.79 (d, 1H), 8.10-8.05 (m. 1H), 7.99 (t, 1H), 7.79-7.68 (m, 2H), 7.44 (m, 1H), 7.20 (d, 1H), 6.94-6.90 (m, 1H), 5.81 (br s, 2H), 3.00-2.90 (m, 4H), 2.46 (m, 4H), 2.26 (m, 1H), 1.79 (m, 2H), 1.60-1.51 (m, 4H), 1.34 (m, 2H) ppm; MS (ES) 523.45 (M+H); 1-(6,7-dimethoxyquinazolin-4-yl)-A/3-(4-(4-(cyclopentyl)piperazin-1-ylcarbonyl)phenyl)-1/7-1,2,4-triazole-3,5-diamine, compound #206, 1H NMR (DMSO-d6, 300 MHz) 9.25 (s, 1H), 9.07 (s, 1H), 8.79 (s, 1H), 8.10 (br s, 2H), 7.69 (m, 2H), 7.41 (m, 3H), 3.97 (s, 3H), 3.92 (s, 3H), 3.35 (m, 6H), 2.42 (m, 4H), 1.70-1.33 (m, 7H) ppm; MS (ES) 544.5 (M+H); 1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-W3-(4-(4-(cyclopentyl)piperazin-1- ylcarbonyl)phenyl)-1/7-1,2,4-triazole-3,5-diamine, compound #207,1H NMR (DMSO-de, 300 MHz) 9.75 (s, 1H), 8.22 (s, 1H), 7.97 (br s, 2H), 7.73 (d, 2H), 7.39 (d. 2H), 3.43 (m, 6H), 2.41 (m. 4H), 2.37 (s, 3H), 1.74-1.31 (m, 7H) ppm; MS (ES) 538.0 (M+H); 1-(7-methyl-2-chlorothieno[3,2-of|pyrimidin-4-yl)-A/3-(4-((2-(pyrrolidin-1- yl)ethyl)aminocarbony|)phenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #208, 1H NMR (DMSO-d6, 300 MHz) 9.80 (s, 1H), 9.58 (s, 1H), 7.99 (s, 1H), 7.88 (br s, 2H), 7.75 (m, 2H), 7.45 (m, 2H), 3.35 (m, 2H), 2.59 (m, 2H), 2.35 (s, 3H), 2.28 (m, 4H), 1.70 (m, 4H) ppm; MS (ES) 499.0 (M+H); 1-(6,7-dimethoxyquinazolin-4-yl)-/tf3-(3-fluoro-4-(4-piperidin-1-ylpiperidin-1-yl)phenyl)-1H- 1,2,4-triazole-3,5-diamine, compound #209,1H NMR (DMSO-de, 300 MHz) 9.32 (s, 1H), 9.00 (s, 1H), 8.79 (s, 1H), 8.14 (brs, 2H), 7.48 (d,1H), 7.36 (s, 1H), 7.26 (d, 1H), 6.95 (t, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.25 (m, 5H), 2.57 (t, 2H), 2.35 (t, 2H), 1.78 (d, 2H), 1.60 (m, 2H), 1.49 (s, 4H), 1.38 (d, 2H) ppm; MS (ES) 548.17 (M+H); 1-(7-methyl-2-chlorothieno[3,2-of|pyrimidin-4-yl)-W3-(3-fluoro-4-(4-piperidin-1-ylpiperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #210,1H NMR (DMSO-d6, 300 MHz) 9.47 (s, 1H), 8.26 (s, 2H), 7.94 (s, 2H), 7.56 (d, 1H), 7.32 (d, 1H), 7.00 (t, 1H), 3.31 (d, 4H), 2.58 (m, 3H), 2.37 (s, 3H), 2.30 (m, 2H), 1.80 (d,2H), 1,60 (m, 2H), 1.48(s, 4H), 1.38 (d, 2H), ppm; MS (ES) 542.06 (M+); 1-(7-methyl-2-chlorothieno(3,2-c/]pyrimidin-4-yl)-/V3-(3-fluoro-4-(3-diethylaminopyrrolidin-1-yl)phenyl)-1H-1,2,4-trlazole-3,5-diamine, compound #211,1H NMR(DMSO-d6, 300 MHz) 9.30 (s, 1H), 8.25 (s, 1H), 7.91 (s, 2H), 7.54 (d, 1H), 7.27 (d, 1H), 6.75 (s, 1H), 3.12 (s, 2H), 2.36 (m, 3H), 2.04 (s, 2H), 1.73 (s, 2H), 1.50 (d, 2H), 1.22 (s, 1H), 0.96 (m, 8H) ppm; MS (ES) 516.38 (M+); 1-(8-methoxy-5,5-dimethyl-5H-chromeno[4,3-c]pyridazin-3-yl)-/\/3-(3-fluoro-4-(4(4-methylpiperazin-1-yl)piperidln-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #212,1H-NMR (DMSO-d6, 300 MHz) 9.21 (s, 1H), 7.83 (broad s, 2H), 7.75 (s, 1H), 7.44 (d,1H), 7.24 (d, 2H), 6.98 (m, 3H), 3.76 (m, 1H), 2.50-2.60 (m, 9H), 2.29 (m, 2H), 2.13 (s, 3H), 1.79 (m, 1H), 1.50-1.70 (m, 4H), 1.04 (s, 3H), 1.02 (s, 3H) ppm; MS (ES) 615.29 (M+H); 1 -(phenanthridin-6-yl)-/V3-(4-(1 -methylpiperidin-4-yl)phenyl)-1 H-1,2,4-triazole-3,5- diamine, compound #213,1H NMR (DMSO-d6, 300 MHz) 9.31 (d, 1H), 9.04 (br s, 1H), 8.91 (d, 1H), 8.78 (d, 1H), 8.08 (d, 1H), 7.99 (t, 1H), 7.85-7.64 (m, 3H), 7.50 (d, 2H), 7.42 (br s, 2H), 7.08 (d, 2H), 2.92-2.89 (m, 2H), 2.24 (s, 3H), 2.06 (t, 3H), 1.69-1.60 (m, 4H) ppm; MS (ES) 450.58 (M+H); 1-(phenanthridin-6-yl)-/V3-(3-methyl-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #214,1H NMR (DMSO-d6, 300 MHz) 9.46 (d, 1H), 8.92 (d, 1H), 8.89 (br s, 1H), 8.77 (d, 1H), 8.08 (d, 1H), 7.99 (t, 1H), 7.81 (t, 1H), 7.74 (t, 1H), 7.68 (t, 1H), 7.51 (br s, 2H), 7.47 (s, 1H), 7.31 (d, 1H), 6.91 (d, 1H), 2.97-2.94 (m, 2H), 2.59 (m, 4H), 2.57 (m, 2H), 2.24-2.18 (m, 1H), 2.22 (s, 3H), 1.95-1.91 (m, 2H), 1.70 (m, 2H), 1.60-1.50 (m,2H) ppm; MS (ES) 519.45 (M+H); 1-(7-methyl-2-chlorothieno[3,2-c/lpyrimidin-4-yl)-A/3-(3-fluoro-4-(isoindolin-2-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #215,1H NMR (CD30D, 300 MHz) 8.65 (s, 1H), 8.23-8.04 (m, 2H), 7.98-7.65 (m, 4H), 7.46 (m, 1H), 4.53 (m, 4H), 2.44 (s, 3H); MS (ES) 493.01 (M+H); 1-(6,7-dimethoxyquinazolin-4-yl)-/\/3-(3-fluoro-4-(isoindolin-2-yl)phenyl )-1/-/-1,2,4-triazole- 3,5-diamine, compound #216, 1H NMR (CD30D, 300 MHz) 8.78 (s, 1H), 8.74 (s, 1H), 8.50 (m, 1H), 8.12-7.38 (m, 6H), 7.38 (s, 1H), 4.53 (m, 4H), 4.08 (s, 3H), 3.99 (s, 3H); MS (ES) 499.06 (M+H); 1-(4-methylthieno[3,2-(flpyridazin-7-yl)-/V3-(3-methyl-4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine (TFA salt), compound #217, 1H NMR (DMSO-de, 300 MHz) 8.88 (brs, 1H). 8.43 (m, 1H), 7.90 (s, 1H), 7.81 (m, 1H), 7.62 (m, 1H), 7.44 (m, 1H). 7.07 (brs, 1H), 7.04 (m, 1H), 3.51 (m. 3H), 3.00-3.30 (m, 6H), 2.60 (m, 1H), 2.49 (s, 3H), 2.32 (s, 3H), 2.00 (m, 1H), 1.59 (m, 3H), 1.41 (m, 3H), 1.78 (m, 2H) ppm; MS (ES) 516.14 (M+H); 1 -(4-isopropylphenyl)-A/3-(4-morpholinophenyl)-1 H-1,2,4-triazole-3,5-diamine, compound #218, MS (ES) 379.73 (M+H), 377.02 (M-H); 1-(7-methyl-2-chlorothieno[3,2-c/]pyrimidin-4-yl)-W3-(7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1W-1,2,4-triazole-3,5-diamine, compound #219, 1H NMR(DMSO-de, 300 MHz)9.31 (s, 1H), 8.26 (s, 1H), 7.91 (brs, 2H), 7.47 (m, 1H), 7.38 (m, 1H), 7.05 (m, 1H), 2.82 (m, 7H), 2.36 (s, 3H), 1.80 (m. 4H), 1.71 (m, 3H) ppm; MS (ES) 496.1 (M+H); 1-(6,7-dimethoxyquinazolin-4-yl)-A/3-(7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H- benzo[7]annulene-2-yl)-1W-1,2,4-triazole-3,5-diamine, compound #220,1H NMR (DMSO-de, 300 MHz) 9.21 (s, 1H), 9.06 (s, 1H), 8.80(s, 1H), 8.11 (brs, 2H), 7.55 (m, 1H), 7.35 (s, 1H), 7.20 (s, 1H), 6.98 (m, 1H), 3.98 (s, 3H), 3.93 (s, 3H), 2.71 (m, 7H), 2.17 (m, 3H), 1.80 (m, 4H), 1.44 (m, 3H) ppm; MS (ES) 501.2 (M+H); 1 -(7-methyl-2-chlorothieno[3,2-c(]pyrimidin-4-yl)-/\/3-(7-(N-methyl-N-bicyclo[2.2.1 Jheptan-2-yl)amino-6,7,8,9-tetrahydro-5W-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #221,1H NMR (DMSO-d6, 300 MHz) 9.38 (s, 1H), 8.23 (s, 1 Η), 7.93 (brs, 2Η), 7.52 (m, 1H), 7.42 (m, 1H). 7.11 (m, 1H), 3.86 (m, 1H), 3.55 (m, 1H), 3.27 (m, 1H), 2.78 (m, 5H), 2.64 (m, 2H), 2.36 (s, 3H), 2.27 (m, 3H), 2.06 (m, 4H), 1.80-1.13 (m, 10H) ppm; MS (ES) 549.1 (M+H); 1 -(7-m8thyl-2-chlorothieno[3,2-c/Jpyrimidin-4-yl)-A/3-(7-(N-bicyclo[2.2.1 ]heptan-2- yl)amino-6,7,8,9-tetrahydro-5/-/-benzo[7]annulene-2-yl)-1AY-1,2,4-triazole-3,5-diamine, compound #222,1H NMR (DMSO-d6, 300 MHz) 9.40 (s, 1H), 8.24 (s, 1H), 7.93 (brs, 2H), 7.47 (m, 2H). 7.11 (m, 1H), 3.42 (m, 1H), 3.24(m, 1H), 2.80 (m, 4H), 2.64 (m, 2H), 2.37 (s, 3H), 2.31 (m, 4H), 1.69 (m, 2H)„ 1.51-1.11 (m, 9H) ppm; MS (ES) 535.1 (M+H); 1-(6,7-dimethoxyquinazolin-4-yl)-A/3-(7-(N-bicyclo[2.2.1]heptan-2-yl)amino-6,7,8,9- tetrahydro-5AY-benzo[7]annulene-2-yl)-1 /-/-1,2,4-triazole-3,5-diamine, compound #223,1H NMR (DMSO-d6, 300 MHz) 9.25 (s, 1H), 9.06 (s, 1H), 8.82 (s, 1H), 8.14 (br s, 2H), 7.56 (m, 1H). 7.37 (s, 1H), 7.21 (s, 1H), 7.01 (m, 1H), 3.99 (s, 3H), 3.93 (s, 3H), 3.40 (m, 1H), 3.23 (m, 1H), 2.73 (m, 4H), 2.43 (m, 1H), 2.30 (m, 3H), 1.73-1.11 (m, 11H) ppm; MS (ES) 541.1 (M+H); 1-(6,7-dimethoxyquinazolln-4-yl)-/V3-(7-(N-methyl-N-bicyclo[2,2.1]heptan-2-yl)amino- 6,7,8,9-tetrahydro-5/-/-benzo[7]annulene-2-yl )-1/-/-1,2,4-triazole-3,5-diamine, compound #224,1H NMR (DMSO-de, 300 MHz) 9.25 (s, 1H), 9.06 (s, 1H), 8.81 (s, 1H), 8.14(brs, 2H), 7.57 (m, 1H). 7.37 (s, 1H), 7.23 (m, 1H), 7.01 (m, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.52 (m, 1H), 3.21 (m, 1H), 2.76 (s, 3H), 2.64 (m, 3H), 2.25 (m, 4H), 1.73-1.12 (m, 11H) ppm; MS (ES) 555.3 (M+H); 1 -(7-methyl-2-chlorothieno[3,2-ai]pyrimidin-4-yl)-A/3-(3-methyl-4-(4-(bicyclo[2.2.1 ]heptan-2-yl)piperazin-1-yl)phenyl)-1 AY-1,2,4-triazole-3,5-diamine (TFA salt), compound #225; 1H-NMR (DMSO-de, 300 MHz) 9.14 (s,1H), 8.20 (s, 1H), 7.80 (s, 2H), 7.64 (m, 1H), 7.46 (m, 1H), 7.05 (m, 1H), 3.55 (m, 2H), 3.12 (m, 1H), 2.63 (m, 1H), 2.41 (m, 1H), 2.39 (s, 3H), 2.35 (m ,2H), 2.33 (s, 3H), 2.03 (m, 2H), 1.61 (m, 4H), 1.44 (m, 4H), 1.22 (m, 2H); MS (ES) 550.14 (M+H); 1-(4-methylthieno[3,2-d]pyridazin-7-yl)-A/3-(3-fluoro-4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1 /-/-1,2,4-triazole-3,5-diamine (TFA salt), compound #226; 1H-NMR (DMSO-de, 300 MHz) 9.29 (s, 1H), 8.42 (d, 1H), 7.98 (broad s, 2H), 7.78 (d, 1H), 7.57(m, 1H), 7.31 (m, 1H), 7.00 (t, 1H), 2.95 (m, 4H), 2,84 (s, 3H), 2.49 (m, 5H), 2.30 (m, 2H), 2.14 (m, 1H), 1.71 (m, 2H), 1.10-1.50 (m, 4H), 0.87 (m, 1H); MS (ES) 520.17 (M+H); 1-(2-chloro-6-methoxy-quinoxalin-3-yl)-/V3-(3-fluoro-4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazln-1-yl)phenyl)-1 AY-1,2,4-triazole-3,5-diamine (TFA salt), compound #227; 1H-NMR (DMSO-d6, 300 MHz) 9.19 (s, 1H), 7.96 (d, 1H), 7.50-7.61 (m, 2H), 7.25 (d, 1H), 7.15 (m, 1H), 7.00 (t, 1H), 3.96 (s, 3H), 3.00- 3.60 (m, 10H), 2.58 (m, 1H), 2.48 (m , 2H), 2.28 (m, 1H), 1.96 (m, 1H), 1.55 (m, 1H), 1.37 (m, 2H), 1.18 (m, 1H); MS (ES) 565.14 (M+H); 1 -(6,7-dimethoxy-1 -methylphthalazin-4-yl)-W3-(3-fluoro-4-(4-((1 S.2S.4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 W-1,2,4-triazole-3,5-diamine (TFA salt), compound #228; 1H-NMR (DMSO-d6, 300 MHz) 9.00 (broad s, 1H), 8.60 (s. 1H), 7.83 (d, 1H), 7.52 (s, 1H), 7.28 (d, 1H), 7.06 (t, 1H), 4.05 (s, 3H). 3.96 (s, 3H), 3.37-3.52 (m, 4H), 3.07-3.17 (m, 4H), 2.93 (s, 3H), 2.59 (m, 1H), 2.49 (s, 3H), 2.29 (m, 1H), 1.98 (m, 1H), 1.57 (m, 2H), 1.38 (m, 2H), 1.21 (m, 1H); MS (ES) 574.34 (M+H); 1-(6-phenylpyridazin-3-yl)-/V3-(3-fluoro-4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2- yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound #229; 1H-NMR (DMSO-de, 300 MHz) 9.23 (s, 1H), 8.40 (d, 1H), 8.11 (d, 1H), 7.99 (d, 1H), 7.84 (broad s, 2H), 7.54 (m, 5H), 7.28 (m, 1H), 6.96 (m, 1H), 3.29 (s, 3H), 2.97 (m, 4H), 2.48 (m, 4H), 2.28 (m, 2H), 2.13 (m,1H), 1.70 (m, 1H), 1.46 (m, 1H), 1.34 (m, 1H), 1.13-1.26 (m, 3H), 0.85 (m, 1H); MS (ES) 526.31 (M+H); 1-(4-phenylpyridin-2-yl)-/\/3-(3-fluoro-4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine (TFA salt), compound # 230; 1H-NMR (CDCl3/MeOD-4, 300 MHz) 8.26 (d, 1H), 7.86 (s, 1H), 7.58 (m, 2H), 7.35-7.43 (m, 3H), 7.26 (m, 2H), 7.10 (m, 1H), 6.87 (t, 1H), 3.25 (m, 1H), 3.12 (m, 1H), 2.50 (m, 1H), 2.27 (m, 1H), 1.77-1.94 (m, 4H), 1.38-1.55 (m, 11H); MS (ES) 525.18 (M+H); 1-(4-methylthieno[3,2-d]pyridazin-7-yl)-/V3-(3-chloro-4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (TFA salt), compound #231; 1H-NMR (CDCI3/MeOD-4, 300 MHz) 9.35 (s, 1H), 8.34 (d, 1H), 7.90 (m, 1H), 7.72 (d, 1H), 7.43 (m, 1H), 7.10 (d, 1H), 3.36-3.46 (m, 2H), 2.97-3.21 (m, 9H), 2.50 (m, 1H), 2.39 (s, 3H), 2.20 (m, 1H), 1.90 (m, 1H), 1.50 (m, 2H), 1.31 (m, 2H), 1.10 (m, 1H); MS (ES) 537.16 (M+H); 1-(4-methylthieno[3,2-d]pyridazin-7-yl)-A/3-(3-methyl-4-(4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine, compound #231; 1H-NMR (CDCI3/MeOD-4, 300 MHz) 7.89 (d, 1H), 7.41 (m, 1H), 7.28 (m, 2H), 6.94 (d, 1H), 3.94 (m, 4H), 2.84 (m, 4H), 2.75 (s, 3H), 2.49 (m, 2H), 2.23 (s, 3H), 2.10 (m, 1H), 1.67 (m, 2H), 1.42 (m, 1H), 1.25 (m, 4H), 0.88 (m, 1H); MS (ES) 516.22 (M+H); 1-(7-methyl-2-m-tolylthieno[3,2-d]pyrimidin-4-yl)-W3-(4-(4-(bicyclo[2.2.1]heptan-2- yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound # 233; 1H NMR (DMSO-de, 300 MHz) 9.11 (s, 1 Η, NH), 8.16-8.02 (m, 5H), 7.62 (d, 1H), 7.51-7.32 (m, 2H), 6.91 (m, 2H), 3.32 (s, 3H), 3.04 (m, 4H), 2.87-2.31 (m, 11H), 1.69 (m, 2H), 1.51-1.10 (m, 4H), 0.85 (d, 1H) ppm; MS (ES) 592.13 (M+H); 1-(7-methyl-2-(3-cyanophenyl)thieno[3,2-d]pyrimidin-4-yl)-A/3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound # 234; 1H NMR (DMSO-dei 300 MHz) 9.05 (s, 1H, NH), 8.62 (s, 1H), 8.11 (s, 1H), 7.97 (s, 3H), 7.59 (m, 2H), 7.56 (d, 2H), 6.90 (d, 2H), 3.32 (s, 3H), 3.02 (s br, 4H), 2.48-2.11 (m, 8H), 1.68 (m, 2H), 1.49-1.07 (m, 4H), 0.84 (d, 1H)ppm; MS (ES) 603.07 (M+H); 1-(7-methyl-2-(2-chlorophenyl)thieno[3,2-d]pyrimidin-4-yl)-A/3-(4-(4-((2S)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1^-1,2,4-triazole-3,5-diamine, compound #235; 1H NMR (DMSO-de, 300 MHz) 9.25 (s, 1H, NH), 8.19 (s, 1H), 8.09 (s, 2H, NH2), 7.89 (m, 1H), 7.64 (m, 3H), 7.54 (s, 2H), 7.01 (d, 2H), 3.70-2.96 (m, 11H), 2.59 (s, 1H), 2.58 (s, 4H), 2.28 (s, 1H), 1.97 (m, 1H), 1.59 (m, 2H), 1.39 (m, 1H), 1.18 (Μ, 1H) ppm; MS (ES) 612.21 (M+H), 610.41 (M-H); 1 -(7-methyl-2-benzo[d][1,3]dioxole -5-ylthieno[3,2-d]pyrimidin-4-yl)-A/3-(4-(4-((2S)-bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl )phenyl)-1 W-1,2,4-triazole-3,5-diamine (formic acid salt), compound #236; 1H NMR (DMSO-de, 300 MHz) 9.39 (s br, 2H, NH2), 9.21 (s, 1H, NH), 8.08 (m, 2H), 7.88 (d, 1H), 7.77 (s, 1H), 7.65 (d, 2H), 7.08-6.95 (m, 2H), 6.1 (s, 2H), 3.65 (m, 2H), 3.59-3.38 (m, 3H), 2.58 (s, 1H), 2.27 (s, 1H), 2.02-1.91 (m, 1H), 1.63-1.42 (m, 2H), 1.41-1.18 (m, 2H)ppm; MS (ES) 622.27 (M+H); 1-(7-methyl-2-pyridin-4-ylthieno[3,2-c/]pyrimidin-4-yi)-A/3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)plperazin-1-yl)phenyl)-1 W-1,2,4-trlazole-3,5-diamine (formic acid salt), compound #237; 1H NMR (DMSO-de, 300 MHz) 9.25 (s, 1H, NH), 8.90 (s, 1H), 8.45 (s, 1H), 8.22 (s, 1H), 8.15-8.02 (m, 2H), 7.65 (d, 2H), 7.37 (m, 1H), 7.02 (d, 2H), 3.81-3.42 (m, 4H), 3.29-2.91 (m, 5H), 2.66-2.19 (m, 6H), 1.98 (m, 2H), 1.71-1.32 (m, 4H), 1.21 (d, 1H) ppm; MS (ES) 579.25 (M+H), 577.37 (M-H); 1-(7-methyl-2-(3-(methylsulfonyl)aminophenyl)thieno[3,2-c/|pyrimidin-4-yl)-A/3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 W-1,2,4-triazole-3,5-diamine (formic acid salt), compound # 238; 1H NMR (DMSO-de, 300 MHz) 9.12 (s, 1H, NH), 8.26 (s, 1H), 8.16 (s, 1H), 8.12-8.02 (m, 3H), 7.60 (d, 2H), 7.53 (t, 1H), 7.37 (d, 1H), 6.93 (d, 2H), 3.04 (s br, 8H), 2.56-2.34 (m, 6H), 2.29-2.13 (m, 4H), 1.69 (m, 2H), 1.51-1.06 (m, 4H), 0.86 (d, 1H) ppm; MS (ES) 671.24 (M+H), 669.39 (ΜΗ); 1-(7-methyl-2-(3-(pyrrolidin-1-yl)prop-1-eny|)thieno[3,2-d]pyrimidin-4-yl)-/\/3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 F/-1,2,4-triazole-3,5-diamine (formic acid salt), compound #239; 1-(7-methyl-2-(3-(4-methylpiperazin-1-yI)prop-1-enyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (formic acid salt), compound #240; 1H NMR (DMSO-d6, 300 MHz) 9.04 (s, 1 Η, NH), 8.15-8.02 (m, 4H), 7.58 (d, 2H), 7.05-6.76 (m, 3H), 3.22 (d, 2H), 3.05 (s, 4H), 2.55-2.10 (m, 12H), 1.71 (m, 2H), 1.48-1.05 (m, 6H), 0.82 (d, 2H); MS (ES) 640.36 (M+H), 638.53 (M-H); 1-(7-methyl-2-(3-(morpholin-4-yl)prop-1-enyl)thieno[3,2-d]pyrimidin-4-yl)-/V3-(4-(4-((2S)-bicyclo[2,2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine (formic acid salt), compound #241; 1H NMR (DMSO-d0, 300 MHz) 9.05 (s, 1H, NH), 8.12-8.01 (m, 3H), 7.59 (d, 2H), 7.02-6.78 (m, 4H), 3.59 (m, 4H), 3.21 (d, 2H), 3.04 (s, 4H), 2.56-2.09 (m, 14H), 1.78-1.59 (m, 2H), 1.41 (m, 1H), 1.39-1.08 (m, 4H), 0.85 (d, 1H) ppm; MS (ES) 627.31 (M+H), 625.60 (M-H); 1-(7-methylthieno[3,2-c/|pyrimidin-4-yl )-^-(3-011^0-4-(4-((18,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (TFA salt), compound #242; 1H-NMR (DMSO-de, 300 MHz) 9.52 (br. s, 1H), 8.88 (s, 1H), 8.15-8.12 (m, 3H), 8.04 (m, 1H), 7.53-7.51 (m, 1H), 7.21-7.19 (m, 1H), 3.35 (m, 4H), 3.16 (m, 4H), 2.50 (m, 3H), 2.43 (s, 3H), 2.29 (m, 2H), 1.98 (m, 1H), 1.58 (m, 2H), 1.40 (m, 2H), 1.20-1.18 (m, 1H) ppm; MS (ES) 536.64 (M+H); 1-thieno[3,2-cflpyrimidin-4-yl-N3-(3-chloro-4-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (TFA salt), compound #243; 1H-NMR (DMSO-d6, 300 MHz 9.55 (br. s, 1H), 8.86 (d, 1H), 8.53 (dd, 1H), 8.14 (br. s, 2H), 8.04 (s, 1H), 7.62 (dd, 1H), 7.51 (d, 1H), 7.20 (d, 1H), 3.55-3.49 (m, 4H), 3.32 (m, 2H), 3.18-3.14 (m, 2H), 3.09-3.05 (m, 1H), 2.60 (m, 1H), 2.29 (m, 1H), 2.01-1.98 (m, 1H), 1.58 (m, 4H), 1.40 (m, 3H), 1.21-1.16 (m, 1H)ppm; MS (ES) 522.12 (M+H); 1-thieno[2,3-d]pyrimidin-4-yl-/V3-(3-chloro-4-(4-((is,2S,4R)-bicyclo[2.2.1]heptan-2- yl)piperazin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine (TFA salt), compound #244; 1H-NMR (DMSO-d6, 300 MHz 9.50 (br. s, 1H), 8.81 (s, 1H), 8.34 (d, 1H), 8.22 (br. s, 2H), 7.92 (d, 1H), 7.89 (s, 1H), 7.44 (d, 1H), 7.20 (d, 1H), 3.55-3.49 (m, 4H), 3.32 (m, 2H), 3.18-3.14 (m, 2H), 3.09-3.05 (m, 1H), 2.60 (m, 1H), 2.29 (m, 1H), 2.01-1.98 (m, 1H), 1.58 (m, 4H), 1.40 (m, 3H), 1.21-1.16 (m, 1H) ppm; MS (ES) 523.12 (M+H); 1-(7-methylthieno[3,2-c/J pyrimidin-4-yl)-N3-(3-fluoro-4-(4-((1S,2S,4/:?)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diaminel compound #245; 1H-NMR (DMSO-de, 300 MHz) 9.38 (br. s, 1H), 8.87 (s, 1H), 8.16 (s, 1H), 8.10 (br. s, 2H), 7.64 (d, J= 15.3 Hz, 1H), 7.32 (d, J = 8.4Hz, 1H), 6.99 (t, J = 9.6 Hz, 1H), 2.95 (m, 4H), 2.42 (m, 4H), 2.43 (s, 3H), 2.28 (m, 2H), 2.14(m, 1H), 1.71-1.66(m, 2H), 1.45-1.16(m, 5H), 0.88-0.84 (m, 1H)ppm; MS (ES) 520,01 (M+H); 1-phenyl-N3-(4-(methylaminocarbonyl)phenyl)-Ns-methyl-1 H-1,2,4-triazole-3,5-diamine, compound # 246; 1H NMR (CD3OD, 300 MHz) 7.87 (m, 2H), 7.54 (m, 7H), 7.38 (m, 1H), 3.85 (s, 3H), 2.96 (s, 3H); MS (ES) 323.17 (M+H); 1-phenyl-N3-(4-(ethyloxocarbonyl)phenyl)-Ns-methyl-1 H-1,2,4-triazole-3,5-diamine, compound #247; 1H NMR (CD3OD, 300 MHz) 7.90 (m, 2H), 7.74 (m, 2H), 7.51 (m, 5H), 7.35 (m, 1H), 4.31 (m, 2H), 2.95 (s, 3H), 1.37 (m, 3H); MS (ES) 338.10 (M+H); 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)-N3-(3-fluoro-4-(3-(R)-methyl-4- (bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1f/-1,2,4-triazole-3,5-diamine (TFA salt), compound #248; 1H-NMR (CDCIa/MeOCU, 300 MHz) 8.81 (s, 1H), 7.78 (m, 1H), 7.64 (dd, 1H), 7.42 (s, 1H), 7.22 (m, 1H), 6.96 (t, 1H), 3.42 (m, 1H), 3.30-3.39 (m, 6H), 2.96 (m, 1H), 2.49 (s, 3H), 2.39 (m, 1H), 2.02 (m, 1H), 1.60-1.80 (m, 2H), 1.65 (d, 3H), 1.51 (m, 6H); MS (ES) 534.20 (M+H); 1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-A/3-(3-fluoro-4-(3-(S)-methyl-4- (bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (TFA salt), compound #249; 1H-NMR (CDCfe/MeOCH 300 MHz) 8.81 (s, 1H), 7.78 (m, 1H), 7.62 (m, 1H), 7.44 (s, 1H), 7.22 (m, 1H), 6.95 (t, 1H). 3.68 (m, 1H), 3.20-3.45 (m, 8H), 2.59 (m, 1H), 2.47 (s, 3H), 2.39 (m, 1H), 2.00 (m, 1H), 1.65 (d, 2H), 1.40-1.80 (m, 6H); MS (ES) 534.20 (M+H); 1-(7-methylthieno[3,2-c(lpyrimidin-4-yl)-A/3-(3-fluoro-4-(3-(R)-methyl-4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (TFA salt), compound #250; 1H-NMR (CDCh/MeOD-4, 300 MHz) 8.65 (s, 1H), 8.25 (s, 1H), 7.62 (s, 1H), 7.46 (d, 1H), 7.05 (d, 1H), 6.80 (t, 1H), 3.55 (m, 1H), 3.00-3.25 (m, 7H), 2.36 (m, 1H) 2.34 (s, 3H), 2.19 (m, 1H), 1.70 (m, 2H), 1.36 (d, 3H),1.20-1.40 (m, 6H); MS (ES) 534.20 (M+H); 1-(7-methylthieno[3,2-c/lpyrimidin-4-yl)-W3-(3-fluoro-4-(3-(S)-methyl-4-((1SI2S,4R)- bicyclo[2.2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1 H-1 ,2,4-triazole-3,5-diamine (TFA salt), compound #251; 1H-NMR (CDCl3/MeOD-4, 300 MHz) 8.46 (s, 1H), 8.21 (s, 1H), 7.45 (s, 1H), 7.29 (d, 1H), 6.90 (d, 1H), 6.64 (t, 1H), 3.35 (m, 1H), 2.95-3.10 (m, 7H), 2.31 (m, 1H), 2.16 (s, 3H), 2.10 (m, 1H), 1.73 (m, 1H), 1.53 (m, 1H), 1.33 (d, 3H), 1.20-1.40 (m, 6H); MS (ES) 534.24 (M+H); 1 -(7-methylthieno[3,2-GQpyrimidin-4-yl)-A/3-(3-methyl-4-(4-((1 S,2S,4ft)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (TFA salt), compound #252; 1H-NMR (DMSO-de, 300 MHz) 9.22 (s, 1H, exchanges with D20), 8.87 (s, 1H), 8.15 (s, 1H), 8.07 (broad s, 2H, exchanges with D20), 7.66 (m, 1H), 7.45 (m, 1H), 7.03 (d, 1H), 3.51 (m, 6H), 3.00-3.25 (m, 4H), 2.61 (s, 1H), 2.49 (s, 2H), 2.43 (s, 3H), 2.31 (s, 3H), 1.99 (m, 1H), 1.59 (m, 1H), 1.38 (m, 1H), 1.22 (m, 1H); MS (ES) 516.32 (M+H); 1-(7-methylthieno[3,2-d)pyrimidin-4-yl)-A/3-(3-methyl-4-(3-(S)-methyl-4-((1S,2S,4R)-bicyclo [2.2.1 ]heptan-2-yl)piperazin-1 -yl )phenyl)-1W-1,2,4-triazole-3,5-diamine (TFA salt), compound #253; 1H-NMR (DMSO-d6, 300 MHz) 8.91 (s, 1H), 8.85 (s, 1H), 8.10 (s, 1H), 7.92 (s, 2H), 7.59(m, 1H), 7.42(m, 1H), 7.00(m, 1H), 2.98 (m, 1H), 2.80 (m, 4H), 2.65 (m , 2H), 2.55 (m, 1H), 2.49 (m, 1H), 2.45 (s, 3H), 2.32 (s, 3H), 2.25 (m, 1H), 2.14 (m, 1H), 1.70 (m, 2H), 1.20-1.50 (m, 4H), 1.15 (d, 3H), 0.82 (m, 1H); MS (ES) 530.70 (M+H); 1-(7-methylthieno[3,2-c(lpyrimidin-4-yl)-/\/3-(3-methyl-4-(3-(R)-methyl-4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine (TFA salt), compound #254; 1H-NMR (DMSO-d6, 300 MHz) 9.14 (broad s, 1H), 8.83 (s, 1H), 8.16 9s, 1H), 8.12 (s, 1H), 8.08 (broads, 2H), 7.60 (m, 1H), 7.43 (m, 1H), 7.01 (m, 1H), 2.85 (m,2H), 2.52 (m, 1H), 2.43 (s, 3H), 2.32 (s, 3H), 2.15 (m, 1H), 1.60-1.80 (m,2H), 1.30-1.50 (m, 2H), 1.10-1.30 (m, 9H), 1.03 9d, 3H), 0.95 (m, 1H); MS (ES) 530 (M+H); 1-thieno[3,2-c/|pyrimidin-4-yl-/\/3-(3-fluoro-4-(3-(S)-methyl-4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 /-/-1,2,4-triazole-3,5-diamine (TFA salt), compound #255; 1H-NMR (DMSO-d6, 300 MHz) 9.50 (s, 1H), 9.10 (broad s, 1H), 8.85 (s, 1H), 8.54(d, 1H), 8.13 (s, 1H), 7.71 (d, 1H), 7.61 (d, 1H), 7.33 (m, 1H), 7.06 (t, 1H), 3.66 (m, 1H), 3.00-3.50 (m, 5H), 2.56 (m, 1H), 2.48 (s, 3H), 2.30 (m, 1H), 1.94 (m, 1H), 1.22-1.63 (m, 9H); MS (ES) 520.28 (M+H); 1-(2-chloro-6-methoxy-quinoxalin-3-yl)-W3-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine, compound # 256; 1H-NMR (CDCl3/MeOD-4, 300 MHz) 9.21 (s, 1H), 7.84 (d, 1H), 7.28-7.41 (m, 2H), 7.24 (m, 1H), 7.12 (m, 1 Η), 6.89 (t, 1H), 3.90 (s, 3H), 3.78 (m, 4H), 3.30 (m, 2H). 2.63 (m, 4H), 2.18 (m, 1H), 1.93 (m, 2H), 1.78 (m, 4H); MS (ES) 538.14 (M+H); 1-(2-chloro-7-methylthieno[3,2-c/|pyrimidin-4-yl)-A/3-(3-methyl-4-(3-(S)-methyl-4- ((1 S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1/-/-1,2,4-triazole- 3,5-diamine (TFA salt), compound #257; 1H-NMR (DMSO-de, 300 MHz) 9.59 (s, 1H), 9.02 (broad s, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.66 (m, 1H), 7.32 (m, 1H), 7.07 (t, 1H), 3.68 (m, 1H), 3.50 (m, 1H), 3.23-3.33 (m, 5H), 2.56 (m, 1H), 2.38 (s, 3H), 2.30 (m, 1H), 1.97 (m, 1H), 1.51 (d, 3H), 1.35-1.60 (m, 6H), 1.24 (m, 1H); MS (ES) 568.21 (M+H); 1-(6-phenylpyridazin-3-yl)-Ai3-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-1H- 1,2,4-triazole-3,5-diamine (TFA salt), compound #258; 1H-NMR (CDCl3/MeOD-4, 300 MHz) 7.92-8.06 (m, 4H), 7.47-7.57 (m, 4H), 7.11 (m, 1H), 6.93 9t, 1H), 3.42 (m, 4H), 3.17 (m, 2H), 2.78 (m, 2H), 1.94-2.16 (m, 6H); MS (ES) 500.22 (M+H); 1 -(4-phenylpyridin-2-yl)-A/3-(3-fluoro-4-(4-(pyrrolidin-1 -yl)piperidin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine (TFA salt), compound #259; 1H-NMR (CDCIa/MeOD-4, 300 MHz) 8.29 (d, 1H), 7.89 (s, 1H), 7.60 (d, 2H), 7.36-7.45 (m, 3H), 7.29 (d, 2H), 7.06 (m, 1H), 6.85 (t, 1H), 3.40 (m, 2H), 3.26 (m, 1H), 3.07 (m, 6H), 2.66 (t, 2H), 1.90-2.00 (m, 6H); MS (ES) 499.14 (M+H); 1-(7-methylthieno[3,2-£/|pyrimidin-4-yl)-W3-(3-fluoro-4-(4-(2-azabicyclo[2.2.1]heptan-2-yl)piperidin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine (TFA salt), compound #260; 1H-NMR (DMSO-d6, 300 MHz) 9.43 (br. s, 1H), 8.87 (s, 1H), 8.15 (s, 1H), 8.12 (br. s, 2H), 7.65 (d, J= 15.3 Hz, 1H), 7.34 (d, J-9.0 Hz, 1H), 7.03 (t, J = 9.3 Hz, 1H), 3.55 (m, 4H), 3.35-3.20 (m, 3H), 2.71-2.65 (m, 1H), 2.43 (s, 3H), 2.28-2.26 (m, 3H), 2.05-1.92 (m, 4H), 1.74-1.69 (m, 4H) ppm; MS (ES) 520.24 (M+H); 1-(7-methylthieno[3,2-c/|pyrimidin-4-yl)-A/3-(4-(1-(bicyclo[2.2.1]heptan-2-yl)piperidin-4-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine (TFA salt), compound #261; 1H-NMR (DMSO-d6, 300 MHz) 9.38 (br. s, 1H), 8.87 (s, 1H), 8.12 (s, 1H), 8.12 (s, 1H), 8.10 (br. s, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 3.50-3.40 (m, 4H), 3.02 (m, 1H), 2.43 (s, 3H), 2.28-2.26 (m, 1H), 1.98 (m, 6H), 1.58 (m, 4H), 1.41 (m, 4H) ppm; MS (ES) 501.24 (M+H), 499.36 (M-H); 1-(7-methylthieno[3,2-c/|pyrimidin-4-yl)-/V3-(3-fluoro4-(1-((1S,2S,4/?)-bicyclo[2.2.1]heptan-2-yl)piperidin-4-yl)phenyl)-1 W-1,2,4-triazole-3,5-diamine (TFA salt), compound #262; 1H-NMR (DMSO-d6, 300 MHz 9.64 (br. s, 1H), 8.89 (s, 1H), 8.15 (br. s, 3H), 7.68 (d, 1H), 7.39 (d, 2H), 7.20 (t, 1H), 3.06 (m, 4H), 2.60 (m, 1H), 2.43 (s, 3H), 2.29 (m, 1H), 2.02-1.96 (m, 4H), 1.57 (m,4H), 1.40-1.36 (m, 4H), 1.16-1.14 (m, 1H) ppm; MS (ES) 519.68 (M+H); 1-(7-methyl-2-chlorothieno[3I2-c/]pyrimidin-4-yl)-A/3-(8-(2-diethylaminoethyl)-9-hydroxy-ej.e^-tetrahydro-eH-benzoHannulene^-ylJ-IH-l^-triazole-S, 5-diamine, compound #263; 1H NMR (DMSO-de, 300 MHz) 9.43 (s. 1H), 9.24 (s br, 1H), 8.25 (8, 1H), 7.94 (s, 2H), 7.57 (d, 1H), 7.47 (s. 1H), 7.09 (d, 1H), 4.50 (d, 1H). 3.75-3.48 (m, 2H), 3.34-3.07 (m, 5H), 2.89 (m. 1H), 2.61 (m, 1H). 2.47 (s. 3H), 2.36 (m, 2H), 2.10-1.39 (m, 4H), 1.17 (m. 6H) ppm; MS (ES) 541.20 (M+H); and 1-(7-methyl-2-chlorothieno[3.2-c/|pyrimidin-4-yl)-N3-(8-(2-diethylaminoethyl)-9-hydroxy- 6,7I8,9-tetrahydro-5W-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine triflouroacetic acid salt (TFA salt of compound # 263); Ή NMR (DMSO-d6, 300 MHz) 9.43 (s, 1H). 9.24 (s br, 1H), 8.25 (s, 1H), 7.94 (s, 2H), 7.57 (d, 1H), 7.47 (s, 1H), 7.09 (d, 1H), 4.50 (d, 1H), 3.75-3.48 (m, 2H), 3.34-3.07 (m, 5H), 2.89 (m, 1H), 2.61 (m, 1H), 2.47 (s, 3H), 2.36 (m, 2H), 2.10-1.39 (m, 4H), 1.17 (m, 6H) ppm; MS (ES) 541.15 (M+H), 539.35 (M-H).

TESTING OF THE COMPOUNDS OF THE INVENTION

The compounds of the invention were tested in the following assay for their ability to inhibit Axl activity.

PHOSPHO-AKT IN-CELL WESTERN ASSAY REAGENTS AND BUFFERS:

Cell culture plate: 96 well assay plate (Corning 3610), white, clear bottom, tissue- culture treated.

Cells: Hela cells.

Starvation medium: For Axl stimulation: 0.5% FCS (fetal calf serum) in DMEM, plus Axl/Fc (extracellular domain of AXL fused to imunoglobulin Fc region) (R&amp;D, 154-AL) 500ng/mL,

For EGF (epidermal growth factor) stimulation: 0.5% FCS in DMEM (Dulbecco's modified Eagles medium).

Poly-L-Lysine 0.01% solution (the working solution): 10pg/ml, dilute In PBS (phosphate buffered saline).

Axl antibody cross-linking: 1st: Mouse anti-Axl (R&amp;D, MAB154). 2nd: Biotin-SP-conjugated AffiniPure goat anti-mouse IgG (H+L) (Jackson

ImmunoResearch #115-065-003 ).

Fixing buffer: 4% formaldehyde in PBS.

Wash buffer: 0.1 % TritonX-100 in PBS.

Quenching buffer: 3% H202i 0.1% Azide in wash buffer, Azide and hydrogen peroxide (H202) are added fresh.

Blocking buffer: 5% BSA in TBST (tris buffered saline plus 0.1% Tween 20).

Primary antibody: Rabbit anti-human Phospho-Akt antibody (Cell Signaling 9271): 1x250 diluted in blocking buffer.

Secondary antibody: HRP (horse radish peroxidase)-conjugated Goat anti-Rabbit secondary, stock solution: Jackson ImmunoResearch (Goat anti-Rabbit HRP, #111-035-144 ) 1:1 diluted in glycerol, store at-20° C. The working solution: 1x 2000 dilution of stock in blocking buffer.

Chemiluminescent working solution (Pierce, 37030): SuperSignal ELISA (enzyme linked immunosorbant assay) Pico Chemiluminescent substrate.

Crystal Violet solution: Stock : 2.5% Crystal violet in methanol, filtered and kept at ambient temperature. The working solution: dilute the stock 1:20 with PBS immediately before use. 10% SDS: working solution: 5% SDS (sodium dodecylsulfate), diluted in PBS METHODS:

Dgy, 1 · A 96 well TC (tissue culture treated) plate was coated with 10pg/mL poly-L-Lysine at 37°C for 30 min, washed twice with PBS, and air-dried for 5 minutes before cells were added. Hela cells were seeded at 10,000 cells/well and the cells were starved in 100 pL starvation medium containing Axl/Fc for 24 hrs. 0972·

The cells were pre-treated with test compounds by adding 100 pL of 2X test compound to the starvation medium on the cells. The cells were incubated at 37°C for 1 hr before stimulation.

The cells were stimulated by Axl-antibody cross-linking as follows: A 5X 1st/2nd Axl antibody mixture was made (37.5pg/mL 1s'/ 100pg/mL 2™*) in starvation medium and nutated at 4°C with thorough mixing for 1-2 hours for clustering. The resulting mix was warmed to 37°C. 50μΙ_ of 5X Axl 1st /2nd of antibody cluster was added to the cells and the cells were incubated at 37°C for 5 min.

After 5 minutes stimulation, the plate was flicked to remove medium and the plate was tapped onto paper towels. Formaldehyde (4.0% in PBS, 100 μΙ_) was added to fix the cells and the cells were Incubated at ambient temperature for 20 min without shaking.

The cells were washed with a plate washer buffer to remove the formaldehyde solution. The plate was flicked to removed excess wash buffer and tapped onto paper towels. Quenching buffer (100 pL) was added to each well and the cells were incubated at ambient temperature for 20 minutes without shaking.

The cells were washed with a plate washer buffer to remove the quenching buffer. Blocking buffer (100 μΙ_) was added and the cells were incubated at ambient temperature for at least an hour with gentle shaking.

The cells were washed with a plate washer buffer and diluted primary antibody (50 pL) was added to each well (blocking buffer was added to the negative control wells instead). The plates were incubated overnight at 4° C with gentle shaking.

Dav 3:

The wash buffer was removed, diluted secondary antibody (100 pL) was added, and the cells were incubated at ambient temperature for 1 hour with gentle shaking. During the incubation, the chemiluminescent reagent was brought to ambient temperature.

The secondary antibody was removed by washing the cells 1X with wash buffer, 1X with PBS by plate washer. The PBS was removed from the plate and the chemiluminescent reagent (80 pL: 40 pL A and 40 pL B) was added to each well at ambient temperature.

The resulting chemiluminescence was read with a Luminomitor within 10 minutes to minimize changes in signal intensity. After reading the chemiluminescence, the cells were washed 1X with wash buffer and 1X with PBS by plate washer. The plate was tapped onto paper towels to remove excess liquid from wells and air-dried at ambient temperature for 5 minutes.

Crystal Violet working solution (60 pL) was added to each well and the cells were incubated at ambient temperature for 30 min. The crystal violet solution was removed, and the wells were rinsed with PBS, then washed 3X with PBS (200 pL) for 5 minutes each. 5% SDS solution (70 pL) was added to each well and the cells were incubated on a shaker for 30 min at ambient temperature.

The absorbance was read at 590 nM on a Wallac photospec. The 590nM readings indicated the relative cell number in each well. This relative cell number was then used to normalize each luminescence reading.

The results of the ability of the compounds of the invention to inhibit Axl activity, when tested in the above assay, are shown in the following Tables wherein the level of activity (i.e., the IC50) for each compound is indicated in each Table. The compound numbers in the Tables referred to the compounds disclosed herein as being prepared by the methods disclosed herein:

All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entireties.

Although the foregoing invention has been described in some detail to facilitate understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims. Accordingly, the described embodiments are to be considered as illustrative and not restrictive, and the invention is not to be limited to the details given herein, but may be modified within the scope and equivalents of the appended claims.

The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

Claims (86)

1. THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

   1. A compound of formula (I):

   wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(Q)N(R6)R7; R2 is aryl optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyi, alkyl, cycioalkyl, cycloalkylalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryi, optionaiiy substituted heteroarylaikyl, optionally substituted heteroarylalkenyl, optionaiiy substituted heterocyclyi, optionally substituted heterocyclylaikyi, optionaiiy substituted heterocyciylalkenyi, -Rs-OR8, -R9-Q-R10-OR8, -R9-O-R10-O-R1c'-OR8, -Rs-O-R10-CN, -R9-O-R10-C(O)OR8, -R9~G-R10-C(G)N(R6)R7, -Rs-O-R10-S(O}pR8 (where p is 0, 1 or 2), -Rs-O-R10-N(R6)R7, -R9-O-R10-C{NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -Rs-C(0)0R8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0R®, -R9-N(R6)C(0)R8, -R9-N(R6)S(0),Rs (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and ”Rs-S(0)tN(R°)R7 (where t is 1 or 2); Ra Is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, haio, haloalkyi, alkyl, cycioalkyl, cycloalkylalkyi, optionally substituted aryl, optionaiiy substituted aralkyl, optionally substituted heteroaryl, optionaiiy substituted heteroarylaikyl, optionaiiy substituted heteroarylalkenyl, optionally substituted heterocyclyi, optionaiiy substituted heterocyclylaikyi, optionally substituted heterocyciylalkenyi, -R9-OR8, -R9-O-R10-OR8, -R9-O-R10-O-R10-GR8, -R9-0-R1Q-CN, -Rs-G-R10-G(O)OR8, -R9-Q-R10-C(Q)N(Rb)R7, -R9-O-R10-S(O)pRs (where p is 0, 1 or 2), -R9-O-R10-N(R6)R7, -Re-O-R10-C(NR11)N(R11)H, -R9-QC(G)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)QR8, -R9-C(Q)N(R6)R7, -R9-N(R6)G{0)0R8, -R^N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0);0Rs (where t is 1 or 2), -Rs~S(0)pR8 (where p is 0, 1 or 2), and ~R9-S(0)«N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aikynyi, haloalkyl, haloalkenyl, haloalkynyi, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyi, optionally substituted cycloaikyl, optionally substituted cycloalkylaikyl, optionally substituted cycloaikylalkenyi, optionally substituted cycioalkylaikynyl, optionally substituted heterocyclyl, optionally substituted heterocyelylalkyl, optionally substituted heterocyclyialkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R1Q-CN, -R10-NO2, "R10"N(RS)2) -R10-C(O)OR8 and ~R10-C{O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W~heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aikynyi, haloalkyl, haloalkenyl, haloalkynyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyi, optionally substituted cycloaikyl, optionally substituted cycloalkylaikyl, optionally substituted cycloaikylalkenyi, optionally substituted cycioalkylaikynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclyialkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched aikenylene chain and an optionally substituted straight or branched aikynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched aikenylene chain and an optionally substituted straight or branched aikynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or--OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof,
2. 2. The compound of Claim 1, which is a compound of formula (la): wherein:

   R\ K4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, ~C(Q)R8 and -C(G}N{RS)R7; R2 is aryl optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyi, alkyl, cycloalkyi, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaryiaikyl, optionally substituted heteroaryiaikenyl, optionally substituted heterocyclyi, optionally substituted heterocyclylalkyl, optionally substituted heterocyciylaikenyi, -Rs-OR8, -R9-G-R,0-GR8, -R9-G-R10-0-R10-OR8, -R9-O-R10-CN, -R9~O-R10-C{O)QRs, -R9~O-R10~C(O)N(Re)R7, -R9-O-R10-S(O)pR8 (where p is 0, 1 or 2), -R9~O-R10~N(R6)R7, -R9-0-R1c-C(NR11}N(R11)H, ~R9-GC(Q)-R8, ~R9~N(R6)R7, -R9~C(0)R8, -R9~C(Q)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)GR8, -R9-N(Re')C(0)R8, ~R9~N(Re)S{0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and ~R9-S(0)tN(R6)R7 (where t is 1 or 2); R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyi, alkyl, cycloalkyi, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaryiaikyl, optionally substituted heteroaryiaikenyl, optionally substituted heterocyclyi, optionally substituted heterocyclylalkyl, optionally substituted heterocyciylaikenyi, -R9-OR8, -R9-O-R10~ORs, -R9-O-R10-O-R10-OR8, -R9-O-R10-CN, -R9-G-R10-C(O)OR8, -R9-Q-R1q-C(0)N(R6)R7, -R9-O-R10-S(O)pR8 (where p is Ο, 1 or 2), -R9~G-R1D~N(R6)R7, -R9-O-R10-C(NR11)N(R11)H, ~Rs~OG(0)-R8, -R9~N(R8)R7, -R9-C(0)R8, -R9-C(0)0R8, -Re-C(0)N(Re)R7, -R9~N(R6)C(G)QR8, -R9-N(R6)C(0)R81 -R9~N(R6)S(G)tR8 (where t is 1 or 2), -R9-S(Q),QR8 (where t is 1 or 2), -R9~S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, aikyl, alkenyl, alkynyl, haloalkyi, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted araikyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloaikylalkyl, optionally substituted cycloalkylaikenyi, optionally substituted cycloalkylaikynyi, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heterocyciylalkenyi, optionally substituted heterocyclylalkynyi, optionally substituted heteroaryl, optionally substituted heteroaryialkyi, optionally substituted heteroaryialkenyi, optionally substituted heteroarylalkynyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)GR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroarvI or an optionally substituted /V-heterocyclyl; each R® is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyi, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloaikylalkyl, optionally substituted cycloalkylaikenyi, optionally substituted cycloalkylaikynyi, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heterocyciylalkenyi, optionally substituted heterocyclylalkynyi, optionally substituted heteroaryl, optionally substituted heteroaryialkyi, optionally substituted heteroaryialkenyi, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenyiene chain and an optionally substituted straight or branched alkvnylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenyiene chain and an optionally substituted straight or branched alkynylene chain; and each Rri is hydrogen, alkyl, cyano, nitro or -OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.
3. 3. The compound of Claim 2 having the following formula (Ia1):

   wherein: R1, R4 and Rs are each Independently selected from the group consisting of hydrogen, alkyl, aryi, aralkyl, -C(0)Rs and -C{0}N(R6)R7; R2a is “R10a“N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted W-heterocyclyi, and R10a is an optionally substituted straight or branched aikyiene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyi, aryl, aralkyl, -R93-OR89, -R9s-C(0)R89, -R"-C(G)GR89, -R"-N(R6s)R79 and R99~C{0)N(R®9)R7g, where each R®9, R79 and R8® is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, aryl and aralkyl, and each R" Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; R3 is selected from the group consisting of aryl and beteroaryi, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyi, alkyl, cycloalkyl, cycioaikylalkyl, optionally substituted aryi, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaryialkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyi, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, ~R9-Q-R1C-0R8, -R9-Q~R10-Q~R10-ORS, -R9-O-R10-CN, -R9-O-R10-G(Q)QR8, -R9-0-R10-G(0)N(R6)R7, -Rs-Q-R10-S{O)pR8 (where p is 0, 1 or 2), -R9~O-Ri0-N{R6)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-OC(G)-Rb, -R9-N(R6)R7, -R9-C(Q)R8, -R9-C(G)0R8, -R9-G(0)N(R6)R7, ~R9-N(R6)C(0)0Rs, ~R9-N(Rs)C(0)R8, -R9-N{R6)S{0)iR8 (where t is 1 or 2), ~R9-S(0)iGR8 (where t is 1 or 2), -R9~S{Q)PR8 (where ρ is 0, 1 or 2), and ~R9-S(0).N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, baioalkenyl, haloalkynyi, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyi, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycioalkylaikyl, optionally substituted cycloalkylalkenyl, optionaily substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyciylalkyi, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionaily substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R1u-OR8, -R'!0-CN, -R10-NO2, -R1Q“N(R8)2, -R10-G(O)QR8 and ~R10-C(O)N(R8)2, or any R6 and R?, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyi, optionally substituted araikynvl, optionally substituted cycloafkyi, optionally substituted cycioalkylaikyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyciylalkyi, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R8 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched aikenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionaily substituted straight or branched alkylene chain, an optionally substituted straight or branched aikenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alkyl, cyano, nitre or-OR8.
4. 4. The compound of Claim 3 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2s is ~R10a-N(R6a)R7a where RSa and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/~heteroaryi or an optionally substituted A/-heterocyclyi, and R10s is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyi, aryl, aralkyl, -R"-GR89, -R"-C{0)RS9, -R"-C{G)QR8s, -R99-N(R6s)R79 and -R"-C(Q)NiR6s)R79, where each R®s, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, aryl and aralkyl, and each R9g is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a monocyclic ary! and a monocyclic heteroaryl, where the monocyclic ary! and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikenyl, -R9-OR8, -R9-OC(G)-R8, -R9-N(R6)R7, -R9-C{0)R8, -R9-C(0)0R8, -R9-C(Q)N(R6)R7, -R9-N(R6)C(0)0R8, -R9~N(R6)C{0)R8, -R9-N(R6)8{G),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6)R? (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyciylaikyl, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, -R1c-OR8, -R10~CN, -R10-NOz, -R10-N(R8)2, -R10-C(O)GR8 and -R10-C(O)N(R8)z, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted /V-heterocyclyl; each R® is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyi, optionally substituted cycloalkyialkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyi, optionally substituted heteroaryl, and optionally substituted heteroarylalkyi; each Rs is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
5. 5. The compound of Claim 4 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted W-heterocyciyl, and R10a is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-QR89, -R"~C(Q)R8a, -R09~C(O)OR89, -R9s-N(R69)R79 and -R9g-C(0)N(R69)R7s, where each R®9, R''9 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a monocyclic aryl optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyi, optionally substituted aryl, optionaliy substituted heteroaryl, optionaliy substituted heterocyclyl, optionaliy substituted heterocyclylaikenyl, -R9-OR8, -RB-GC(0)-Rep -R9~N(R6)R7, -R9-C(Q)R8, -R9-C{G)QR8, -R9~C(Q)N(R6)R7, -R9~N(R6}C(Q)OR8, -R9-N(R6)C{Q)R8, -R9-N{R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)s0R8 (where t is 1 or 2), -Ra-S(G)PR8 (where p is 0, 1 or 2), and -R9~S(G)iN(R8)R7 (where t is 1 or 2); each R6 and R'' is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaikyl, optionally substituted cycloalkyialkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylaikyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyi, -R10-OR8, -R10-CN, ~R10~NG2, -R10-N(R8)2, ~R10~C(G)GR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted /V-heterocyciyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted araikyl, optionally substituted aralkynyl, optionally substituted cycloaikyl, optionally substituted cycloaikylalkyl, optionally substituted heterocyclyi, optionaily substituted heterocyciylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionaily substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
6. 6. The compound of Claim 5 selected from the group consisting of: 1-phenyl-A/3~(4-{2-(pipendin-1-y!)ethoxy)phenyl)-1H-1,2,4-triazoie-3,5-diamine; 1-(4-isopropylphenyi)-/V,'3-(4-{2-(piperidir3-1-yi)ethoxy)phenyl)-1/-/-1,2,4”triazoie-3,5- diamine; 4-(5~amino~3-(4-(2-(pyrrolidin-1-yi}ethoxy)phenylarr!ino)-1H-1I2,44riazoi-1- yl)benzenesulfonamide; 1-(2-fluorophenyl)-A/3-{4-(2-(2-m8thylpyrrol!d!n-1-yl)ethoxy)pheny!)-1H-1,2,4-triazo!e-3:5- diamine; 1-(2~fiuorophenyl)-A/3-{4-(2-(piperid!n-1-yl}ethoxy)phenyl)-1W-1,2,4-triazole-3,5-diamine; and 1-(2-f!uoroph8nyi)-W3-{4-(2-(pyrrolid!n-1-yi)ethoxy)pheny!)-1H-1,2,4-triazole-3,5-diamine.
7. 7. The compound of Claim 4 wherein: R\, R4 and Rs are each independently selected from the group consisting of hydrogen and aikyi; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionaily substituted W-heteroaryl or an optionally substituted /V-heierocyclyi, and R10a is an optionaily substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R90-GR8g, -R9s-C{0)R88, ~R9s~C(0)0R89, ~R99-N(R6s)R79 and -R99-C(0)N(R8s)R7g, where each R6®, R?s and R8® is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R93 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; R3 is a monocyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of halo, haloaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyeiylalkenyl, -R9~QKS, -Rs-GG{0)-R8, ~R9-N(R6)R7, -RS~C(Q)R8, -R9-C(G)QR8, -R9-C(0)N(R6)R7, -R9-N(R6)C{0)0R8, -R9-N(R6)C{0)R8, -R9-N(R6)S(G)tR8 (where t is 1 or 2), -Rs-S(0)t0R® (where t is 1 or 2), -R8-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(G)sN(R6)R7 (where t is 1 or 2); each Rb and R7 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-GR8, -R10-CN, -R10-NO2, ~R10-N(R8)2, -R10-C(O)OR8 and -R10-C{O)N(R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroary! or an optionally substituted /V-heterocyclyl; each R0 is independently selected from the group consisting of hydrogen, aikyi, haloaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heieroaryj, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; and each R10 is an optionally substituted straight or branched aikyiene chain.
8. 8. The compound of Claim 7 selected from the group consisting of: A/3-(3”Chioro-4-(2"(pyrrolidin-1-yl5ethoxy}phenyi)-1-(pyndin“2-yl)-1H-1,2,44riazole-3,5-diamine; 1-(pyridin-2-yl}-/¥3-(4-{2-{pyrrolidin-1-yi)efhoxy)phenyi)-1H-1,2,4-iriazole-3,5-diamlne; /V5-methyl-1 ~{pyridin-2-yl )“Λ/3~(4-(2~{ pyrrol id in-1 -yl)ethoxy)phenyl)-1 /-/-1 ,2,4-triazole-3,5-diamine; N3-(4"(2-(pyrroildlR"1-yl}ethoxy)phenyl)"1-(4-(trifluoromethyl)pyrimidin-2-yl )-1/-/-1,2,4-trlazoie-3,5-diamlne; 1 -(2-ch!oropyridin”4-y!)“A/3-(4-{2~(piperidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazol8-3,5-diamine; 1 -(6"Ghloropyridazin-3-yl)-A/3-(4~(2-(pyrro!idin~1 -yi)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1"{pyraz!n-2-yl}-/V3-(4-{2-(pyrrQiidin-1-yI)etboxy}phenyj}-1H-1,2,4-triazole-3,5-diamine; 1 -{2-morphoiinopyridin-4-yi}-Af3-(4-(2-(pipsndin-1 -yi)etboxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-{6-Gh!Gropyridin”2"yl)“A/s-{4-(2“(pyrrolidin-1-yl)ethoxy)pheny!)-1H-1l2,4”triazoie-3>5- diamine; 1 -(5-ch!Gropyridin"2-yl)”A/3-(4"(2“{pyrrolidin"1-yl)ethoxy)phenyl)"1 H-1,2,4-triazole-3,5-diamine; 1-{3-ch!Gropyridin-2-y!)-/\/3-{4-(2-{pyrrolid!n-1-yl}ethoxy)pheny!)-1H-1>2,4-triazoie-3>5- diamine; 1 -{6-chlGropyridin-2-yl)~A/3-{4-(2"(piperidin-1-y!)ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1 -{6-morphoSinopyridin-2-yi}-A/3-(4-(2-{piperidin-1 -y!}ethoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; A/3-(4-{2-(pyTrQl!d!n-1-yl)ethoxy)phenyi)-1-(4-{trifluoromeihyl)pyridin-2-yl)”1H-1,2,4-triazote-3,5-diamine; /V3-(4-{2-(pyrroIidin-1 -yl)ethoxy)phenyi )-1 -(3-(trif!uoromethyS)pyridin-2-yl )-1/-/-1,2,4-triazole-3,5-diamine; 1-{0-methoxypyrid!n-2-yl}-/V3-(4-(2-(pyrrOiidin-1-y!)ethoxy)phenyl)-1 W-1,2,4-triazole-3,5-diamine; 1-{5-bromopyridin~2”y!)-/V3-(4-{2-(pyrro!idin~1-y!)ethoxy)phenyl}-1H-1J2,4-triazole-3,5- diamine; 1- (6~{methyiamino)pyridin-2~yl)-W5-(4-(2-(piperid!n-1-y1)eihGxy)phenyi)-1H-1,2,4-triazole- 3,5-diamine; 1 -(6~(dimethy!amino)pyridin-2~yl)-W3-{4~C2-(piperidin-1 -yl)ethoxy)phenyl)-1 H-1,2,4-triazo!e-3,5-diamine; 2- (5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1H-1,2,4-triazol-1-yl)-6- methylpyrimidin-4-ol; 1-(pyrimidin-2-yl)-/V3-(4-(2-(pyrrolidin-1-y!)ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; and A/3-(3-fluoro-4-(2-(pyrroiidin-1-yl)ethoxy)phenyl)-1-(pyridin-2-yl)-1H-1,2,4-triazole-3,5- diamine,
9. 9, The compound of Claim 3 wherein: R\ R4 and Rs are each independently selected from the group consisting of hydrogen and alkyl; R2als -R1t>a-N(R6a)R7a where RSa and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted IV-heterocycSyl, and R10a is an optionally substituted straight or branched aikylene chain; R2g is selected From the group consisting of hydrogen, halo, alkyl, haioalkyl, aryl, aralkyl, -R"~GR89, -R99-C(0)RBg, ~R93-C(0)GR8s, -R9s~N(R6s)R7e) and -R"-G{Q)N(R69)R7s, where each R69, R?9 and R89 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, aryl and aralkyl, and each R93 is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heierocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9~QC(G)-R8, -R9-N(R6)R7, -R9-C(G)R8, -R9-C(G)0R8, -R9-C(G)N(R6)R7, -R9~N(R6)C{0)QR8, -R9-R{R6)C(0)R8, “R9-N{R6)S(0)»R8 {where t is 1 or 2), --R9-S(G)tGR8 (where t Is 1 or 2), -R9-S(G)PR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioalkyl, optionally substituted cycloalkyiaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10~OR8, -R10-CN, -R1g~NQ2, -R10-N(R8)2, ~R10-C{O)GR8 and -Ria-C(0}N(R8}2> or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycioalkyl, optionally substituted cycloalkyiaikyl, optionally substituted heterocyclyi, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
10. 10, The compound of Claim 9 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is ~R1Qa~N{R6a)R7a where R6s and R73, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted N-heterocyclyi, and R10a is an optionally substituted straight or branched alkylene chain; R20 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R9'3-OR88, -R9s~C(G)R88, -R9s-C(Q)OR8g, -R9s-N(R6s)K7s and ~R9s~C(G)N(R69)R7s, where each R®9, R70 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a bicyclic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyi, optionally substituted heterocyclylalkenyl, -R9-GR®, -R9~GC(Q)-R8, -R9~N(R8)R7, -R9-C(Q)R6, -R9-C(0)GR8, -R9-C(0)N{R6)R7, -R9-N(R6}C(G)OR8, -R9-N(R6)C(G)Rb, -R9-N{R6)S(OXR8 (where t is 1 or 2), -R8-S(Q).OR8 (where t is 1 or 2), ~R9~S(Q)pR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R' (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloaikyi, optionally substituted oydoalkylalkyl, optionally optionally substituted heterocyclyi, optionally substituted heterocydylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R1d~N(R8)2, -R10-C(O)OR® and ~R10~C(G)N(RS)2, or any Re and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyciyi; each Rs is independently selected from the group consisting of hydrogen, alkyl, haioalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally substituted heterocyclyl, optionally substituted heterocydylalkyi, optionally substituted heteroaryl, and optionally substituted heteroaryiaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
11. 11. The compound of Claim 9 wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and aikyl; R2a is -R1ua-N(R6a)R7a where RSa and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-beteroaryl or an optionally substituted A/-heterocyclyl, and R1tla is an optionally substituted straight or branched alkylene chain; R2® is selected from the group consisting of hydrogen, halo, aikyl, haioalkyi, aryl, aralkyl, -R9s-OR8g, -R9s-C(Q)R8s, ~R"~C(Q)OR89, -R"~N{R6s)R79 and -R99-C{Q)N(R69)R70, where each R®9, R?g and R89 is independently selected from the group consisting of hydrogen, aikyl, haioalkyi, aryl and aralkyl, and each R9s is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a bicyciic heteroaryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocydylalkenyi, -R9-OR8, -R9-0C{Q}-RS, -R3-N{R6)R7, -R9~C(0)R8, -R9-C(0)0RB, -R9-G{0)N(R6)R7, -Rs-N(R6)C(0)0R8, -R9-N(R6)C(G)R8, -R9-N(R6)S{Q)sR8 (where t is 1 or 2), -R9-S(0},0R8 (where t is 1 or 2), -R9~S(0)PR8 (where p is 0, 1 or 2), and -RM-S(0)fN(R6)R7 (where t is 1 or 2); each R6 and R? is independently selected from the group consisting of hydrogen, alkyl, haioalkyi, bydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocydylalkyi, optionally substituted heteroaryl, optionally substituted heteroaryiaikyl, -R10-OR8, -R10-CN, -R10-NO2< -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O}N{R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycioalkyl, optionally substituted cycloaikylaikyl, optionally substituted heterocvclyl, optionally substituted heterocyciylaikyl, optionally substituted heteroaryl, and optionally substituted heteroaryialkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each R10 is an optionally substituted straight or branched alkyiene chain.
12. 12. The compound of Claim 11 selected from the group consisting of: 1-(7-(benzyiGxy)-8-methoxyquinazo]in-4-yl)-A/3-(4-{2-(pyrrolidin-1-yl)ethoxy)phenyl}-1/-/- 1,2,4-triazole-3,5-diamine; A/3-(4-(2^yrroiidin"1~yi)ethoxy)pbeny!)-H'quinoxaiin-2~yl)-1H-1>2I4-tria20le-3>5“diamine; 1~(benzo[<^thlazoi-2-yl)-W344-{2-(pyrroildin-1 -yl}ethoxy)phenyi}· 1/4-1 :2,4-triazc>ie-3,5-diamine; 1-(1-methyl-1 H"benzo[cf|imidazoi"2-yl)"A/3-(4-{2"(pyrrolidin-1-yi}ethoxy)pheny! )-1 H-1,2,4-triazoie-3,5-diamine; A/3-(4-(2-(2-mefhy!pyrrolidin-1-yl)etboxy)phenyl)-1-iquinoxalin-2-yl)-1/7-1,2,4-iriazole-3,5- diamine; Hbenzotcflthiazol^-yO-W^-^-^-methylpyrrolidin-l-ylJethoxyJphenylMH-l^^- triazole-3,5-diamine; 1-(1-methy!-1H-beπzo[c/]imίdazol·2-yi)-,fV'3!-(4-(2-(2-methylpyrrol!d!n-1-yί)ethoxy)phenyl)-1/4-1,2,4-iriazoie~3,5-diamine; 1 -(1 H-benzo[d]imidazoi-2~yl)-iV3-(4-(2-(2-methylpyrroiidin-1-yi)ethoxy)phenyi )-1 /4-1,2,4-triazole-3,5-diamine; 1-(phthalazi n-1-yl)- A/i'-(4-(2-(pyrrolidin-1~yl)ethoxy)phenyS )-1 HA ,2,4-trigzoie-3,5-diamine; 1-(1H-benzo[d]ίmidazol·2~yl)-A/3-(4~{2-(pyrroiidin~1-yi)ethoxy)ρhenyl)-1f7-1,2,4-triazole- 3,5-diamine; methyl 1-(2-(4-(5-amino-1-(quinoxalin-2-yl)-1H,-1,2,4-triazol-3- y!amino)phenoxy)ethyi)pyrro!idine-2-carboxylate; 1-{2-ohtoroqujnaz:o!!n-4“y!}-W3-(4"(2-(pyrrol!din-1-y!)ethoxy)phenyi}-1/-f1!2,4-iriazole-3,5- diamine; 1 -(2-morpho!inoquinazoSin-4-yi)-/V3-{4-(2-{pyrroiidin-1 -y!)ethoxy)phenyl)-1 H-1,2,4-triazoie- 3.5- diamine; 1~{benzo[d]thiazol-2-y1)-/V3-{3-chioro-4-(2-(pyrroIidin-1-yi)ethoxy)phenyl}-1H-1,2,4- triazoie-3,5~dSamine; /^-{S-chlorc^^-ipyrrclidin-l-yOethoxyiphenylH-fl-methyl-IW-benzoIe/limidazol^-yl)-1H-1,2,4-triazole-3,5-diamine; 4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(quinolin-2-yl )-1/4-1,2,4-triazole-3,5-diamine; methyl 1-(2-(4-(5-amino-1-(benzo[of]thiazol-2-yl)-1 H-1,2,4-triazol-3-ylamino)phenoxy)ethyl)pyrrolidine-2-carboxylate; 1-{2-chioro-6!7-dimeihoxyquinazoSin-4-yl)-A/3-{4-(2-(pyrroifdin-1-yl)ethoxy)phenyl)-1H- 1,2,4-triazola-3,5-diamine; 1“(6,7-dimethoxyquinazo!!n-4-yS)-IV3-(4-(2-(pyrrolidin-1-yl)ethoxy}pheny!}”1/7"1,2>4-triazole-3,5-diamine; A/3-(4-{2-(2,5-dimethylpyrrolidin-1 -yl)ethoxy)phenyl)-1 -(quinoxalin-2-yl)-1 H-1,2,4-triazole- 3.5- diarnine; 1-(6-chioroqusnazoiin-4-y!)-A/3-(4-(2-(pyrrolidin-1-yi}ethoxy}phenyi)-1 H-1,2,4-triazole-3,5-diamine; 1-{2-ch!oro-6!7-dihydro-5H-cyciopenta[d]pyrinr!idir!-4-yi)-/V3-(4-(2-(pyrroiidin-1-yi)ethoxy)phenyi)-1 H-1,2,4-triazole-3,5-diamine; 1 ~(isoquino!in~1 -yi)-A/3-(4~(2-(pyrrolidin-1 -yl)ethoxy)phenyi )-1 H-1,2,4-triazole-3,5-diamine; /V3-{4-(2-(pyrrolidin-1-yi)ethoxy)phenyl)-1-(thieno[2,3-d|pyrim!din-4-yl}-1H-1!2,4-triazole- 3.5- diamine; 1-(6-phenylthieno[3,2-d|pyrimidin-4-yl)-yV3-(4-(2-(pyrTolidin-1-yl)ethoxy)phenyl)-1H-1,2,4- triazole-3,5-diamine; A/3-(4-(2-(pyrro!idin-1-yi)ethoxy)phenyi)-1-(2-{trifluoromethyl)quinazoiin-4-yi )-1 H-1,2,4-triazo!e-3,5-diamine; A/5-(4-(2-(pyrro!idin-1 -yi)ethoxy)phenyl)-1 -(thieno[3,2-cf] pyri m i d in-4-yl)-1 H~1,2,4-triazole- 3.5- diamine; /V3-(3-fluoro-4-(2-(pyiTolidin-1-yl)ethoxy)phenyl}-1-(quinoxalin-2-yl)-1f/-1,2,4-triazole-3,5- diamine; 1-(benzo[d]thlazoi-2-yl}-W3-{3-f!uoro-4-(2~(pyrro!idin-1-yi}ethoxy)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(2-ch!oro-7~m8thyithi8no[3,2-cfJpyrimidin~4-y!}"W3-(4-{2"(pyrrolidin-1-y08thoxy)phenyl)-1 H~ 1,2,4-triazoie-3,5-diamine; W3-(3~f!uoro~4-(2~(pyrro!idin-1-yl)eiboxy)phenyi)-1-(isoqu!nolin-1-y!)-1f/~1,2l4-triazoie~3,5~ diamine; A/3-(3-chloro-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(6l7-dimethoxyquinazolin-4-yl)-1H- 1.2.4- triazole-3,5-diamine; A/3-(3-chioro~4-(2-(pyrroiidiR-1-yi)ethoxy)phenyl)-1-(isoquino!in-1-y!)-1/-/~1,2l4”triazole~3,5"· diamine; 1-{6-fluoroquinazoiin-4-yi)-A/3~(4-{2-(pyrroIidir5-1~yl)sthoxy)pheny!)-1W-1,2,4-iriazofe-3,5- diamine; A^-{4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1-(thieno[2,3-c]pyridin-7-yl)-1/-/-1l2,4-triazole-3,5- diamine; 1-(2-methylquinazo!in-4-yi)-/V3-(4-(2~(pyrroiidin-1-yI)ethoxy)phenyi)-1H-1l2,4-triazoie-3,5- diamine; 1- (furo[3,2-c]pyrid!n-4-yi)-W3-(4-{2-{pyrroiidin-1-yl)ethoxy)phenyi)-1H“1!2>4-triazole-3l5" diamine; 2- ( 5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1H-1)2I4-triazol-1-yl)-5,6,7,8- tetrahydroquinazoiin-4“Oi; 1 -(6,7-dimethoxyisoquinoiin-1~yl)-W3-(4-(2-(pyrroiidin-1-yi)ethoxy)pheRyl )-1 /7-1,2,4-iriazoie-3,5-diamine; 5-(5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1/-/-1,2,4-triazol-1-yl)-1,6- naphthyridin-2(1H}-one; benzyi 3-(5-amino-3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)-1f/-1,2,4-triazol-1-yl)-7,8- dihydropyrido[4,3-c]pyridazine~6(5H)-carboxylate; A/3-(4-(2-(pyrrolidin-1-y!)ethoxy)pbenyl)-1-(5,6I7,8-tetrahydropyrido[4,3-c]pyridazin-3-y!)-1 Η-1 ^^-triazoIe-S.S-diamine; 1-(2l6-dieh!orothieno[3,2~c/]pyriniid!n-4-yi)~A/3-(4-(2-pyrroiidin~1-yteihoxy)pheny!)-1H~ 1.2.4- triazole-3,5-diamine; 1-(2-chioroihieno[2,3-d]pyrimidin-4-yi)-A/l'-(4~(2-pyrrolidin-1-yiethoxy)pheny!)-1H-1,2,4-iriazole-3s5-diamine; and 1-(2-chiorothieno[3,2-d3pyrim!din-4-yi)-W3-(4-(2-pyrroHdin-1-yiethoxy)phenyl)~1H-1,2,4- triazole-3,5-diamine.
13. 13. The compound of Claim 3 wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N{R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryi or an optionally substituted A/-heterocyclyl, and R1ua is an optionally substituted straight or branched alkylene chain; R2s is selected from the group consisting of hydrogen, halo, alkyl, haloalkyi, aryl, aralkyl, ~R9s~OR89, -R99-C(0)R89, -R9s-C(G)QRB9, ~R"-N(Re9)R79 and -R9s-C(0}N(R6s)R79, where each R69, R73 and RSs is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, any! and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of a tricyclic aryi and a tricyclic heteroaryl, where the tricyclic aryi and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyl, alkyl, optionally substituted aryi, optionaiiy substituted heteroaryl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkenyl, -R9-GR8, -R9-QC{G)~R8, -R9~N(R6)R7, -R9-C(0)R3, -R9-C(G)QR8, -R9-C(0)N{R6)R7, -R9-N(R6)C(0}0R8, -R9-N(R6)C{0)R8, -R9~N{R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)tQR8 (where t is 1 or 2), -R9~S(G)PR8 (where p is 0, 1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alky!, haioalkyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally optionally substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionaiiy substituted heteroarylalkyl, ~R10-QR8, -R10-CN, ~R10~NO2, -R10-N(R8)2, -R10-C(O)OR8 and ~R1D-C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocyclyl; each R8 Is independently selected from the group consisting ot hydrogen, alkyl, haioalkyl, optionally substituted aryi, optionaiiy substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyi, optionally substituted cycloalkylalkyi, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionaiiy substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
14. 14. The compound of Claim 13 wherein: R1, R4 and R5 ar© each independently selected from the group consisting of hydrogen and alkyl: R2a is -R10a-N(R6a)R7a where R6a and K7a, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heieroaryi or an optionally substituted W-heterocyc!yl, and R10a is an optionally substituted straight or branched alkylene chain; R2g is selected from the group consisting of hydrogen, halo, alkyl, haloalkvl, aryl, aralkyl, ~R"~OR8g, -R9s-C(G)R89, -R"-C(0)0R8a, -R9s-N(R69)R7s and -R"-C(G}N(R89)R7s, where each R®9, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a tricyclic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyi, optionally substituted heterocyclylalkenyl, -R9~OR8, -RS-QC(G)~R8, -R9-N(Re)R7, -RS-C(Q)R8, -R9-C(0}GRs, -R9-C(0)N{R6)R7, ~R9-N(R6)C(0)0R8, -R9-N{R6)C{G)R8, “R9-N(R6)S(0)tR8 (where t is 1 or 2), -Rs-S{G)tOR8 (where t is 1 or 2), -R9-S(Q)PRB (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each Rs and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalky!, optionally substituted cycloalkyiaikyi, optionally optionally substituted heterocyclyi, optionally substituted heterocyclyiaikyl, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, -R10-QR8, -R10-CN, -R10-NO2, -Rk-H(R8)2, ~R10-C(O)OR8 and -Ri0-€(O)N(R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroary! or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, aikyl, haloalkyl, optionally substituted aryl, optionally substituted araikyi, optionally substituted aralkynyl, optionally substituted cycloaikyi, optionally substituted cycloalkylalkyl, optionally substituted beterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each Rs is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.
15. 15. The compound of Claim 13 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N(R6a}R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched aikylene chain; R?'8 is selected from the group consisting of hydrogen, halo, alkyl, haioalkyl, aryl, aralkyl, -R"-QR8s, ~R"-C{G)R89, -RS9-C(0)0R89, -R9s-N(R69)R79 and -R9g-C(Q)N{R69)R7s, where each R69, R73 and R8® is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, aryl and aralkyl, and each R99 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R3 is a tricyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted beterocyclyl, optionally substituted heterocyciyialkenyl, -R9-QR8, -R9-QC(0)-R8, -R9~N(R6)R', -R9-C(G)R8, -R9~C(0)0R8, -R9~C(G)N(R6)R7, -R9~N(R6)C{0)0R8, -R9-N(R6)C(Q)R8, ”R9-N{R6)S(G)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)PR8 (where p is 0, 1 or 2), and -R9~S{Q),N(R8)R' (where t is 1 or 2); each Re and R7 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, bydroxyaikyi, optionally substituted aryl, optionally substituted araikyi, optionally substituted cycloaikyi, optionally substituted cycloalkylalkyl, optionally optionaliy substituted heterocydyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylaikyi, -R1G-OR8, -R10-CN, -R10-NO2, -R10-!M{R8}2, -R10-C(O)GR8 and -R10~C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroary! or an optionally substituted W-beterocyclyi; each R8 Is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyi, optionally substituted heterocyclylaikyi, optionally substituted heteroaryl, and optionally substituted heteroaryiaikyl; each R9 Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
16. 16. The compound of Claim 15 selected from the group consisting of; 1-(5,6,6a,7,8,9,10,10a-octahydrobenzo[ft]quinazolln-2-yl)-/V3-(4-(2-(pyrrolidin-1- y!)ethoxy)phenyl)~1 H-1,2,4-triazole-3,5-diamine; 1 -(5,δ-dihyd rabenzG[fr]quinazolin-2~y!)~/V3-(4~(2-(pyrrolidin-1 -yl)ethoxy)pbenyi )-1 H-1,2,4-triazole~3,5-diamine; /^-(4-(2-(pyrrolidin-1~yi)ethoxy)phenyi )-1-(6,7,8,9-tetrahydro~5/·/- cyciohepta[4,5]thieno[2,3-c/]pyrimidin-4-yl)-1 Η-Ί, 2,4-triazoie-3,5-diamine; 1~(5,6,7I8-tetrahydrQbenzo[4,5]thienG[2,3~d]pyr!rnidin~4~yi)~/V3-(4~(2~(pyrrolidin~1-yl)ethoxy)phenyl)~1 H-1,2,4-triazole-3,5-diamine; 1-(6,7-dihydro-5H-cydopentat4,5]thieno[2,3-dipyrimidin~4-yl)~/V3-(4-(2-{pyrrol!din-1-yl)efhoxy)phenyl)-1 H-1,2,4-triazole-3,5-diamine; A/3-(3-chloro-4-(2-(pyrrolidin-1 -yi)ethoxy)phenyi)~1-(5,6,7,8- tetrahydrobenzo[4,5]thieno[2,3-c/]pyrimidin-4-yl )-1 tf-1,2,4-tri azole-3,5-diamine; A/3-(3-fluoro-4-(2“(pyrrolidin-1-yl)ethoxy)phenyl)“1-(5)6,7,8- tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl )-1/-/-1,2,4-triazoie-3,5-diamine; 1-(2-methyl·5,6,7,8-tetrahydrobenzo[4.5]thieno[2!3-£/]pyr!midin-4-yl)-A/3-(4-(2-(pyrrol!din-1-yl)ethoxy)phenyl )-1 H-1,2,·4-triazole-3,5-diamine; 1-(benzothieno[3,2-c/|pynmidin-4-yl}-W'3-(4-(2-(pyrrolidin-1-yl)ethoxy)pheny!)-1H-1,2,4-triazole-3,5-diamine; 1“(7-ferf-butyl-5,6,7,8"tetrahydrobenzo[4>5]thieno[2,3-djpyrim!din-4-yl)-A/'J-(4-(2-(pyrroiidin-1 -yl)ethoxy)phenyi)-1 W-1,2,4-triazoie-3,5-diamine; and 1 -(5,6-dihydrobenzo[/)]cinnolin-3-yl)-A/3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyi)-1H-1,2,4-trlazoie-3,5-diamine.
17. 17. The compound of Claim 2 having the following formula (Ia2);

    wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, ~C(0)R8 and -C(G)N(R8)R7; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C{0)GR8b, -R9b-N(R6b)R7b and -R9b-C(G)N(R6b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylerse chain; R2cis selected from the group consisting of -C{G)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalky! and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyi, cycioaikylaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryi, optionally substituted heteroarylaikyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heierocyclyiaikenyl, -R9-OR®, -R9~0-R10~GR8, -R9-O-R!0-O-Ri0-OR8, -R9-G-Rl0-CN, -R9-O-R10-C(O)OR8, -R9-O-R10-C(O)N(R6)R7, ~R9-Q~R10-S(O)pR8 (where p is 0, 1 or 2), -R9-0-R1D-N(R8)R7, ~R9-Q-R10-C(NR11)N(R11)H, -R9-0C(Q)~R8, ~R9~N(Rs)R7, ~R9~C(0)R8, ~R9~C(0)0R8, ~R9-C(G)N(R6)R7, -R9-N(R6)C(G)QRs, -R9-N(R6)C(0)R8, -R9-N(R6)SiO),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(Q)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each RD and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyi, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkyialkynyl, optionaliy substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heierocyciyialkenyl, optionally substituted beterocyclyiaikynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryiaikynyi, -R10-ORe, -R10-CN, -R10~NO2, -R10-N(R8}2, -R10-C(O)OR8 and -R10-G{Q)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyi, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycioalkyialkenyi, optionally substituted cycloalkyialkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heterocyclylaikenyi, optionally substituted beterocyclyiaikynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryiaikynyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; each R10 is an optionally substituted straight or branched alkylene chain; and each R11 is hydrogen, alkyl, cyano, nitre or-OR8.
18. 18. The compound of Claim 17 wherein: R1, R4 and R° are each independently selected from the group consisting of hydrogen and alkyl; Rib is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OK8b, -R9b-C(G)QR8b, ~R9b~N(RSb)R7b and -R9b-C{0)N(R6b)R7b, where each R6b, R7b and RBb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is selected from the group consisting of -C{0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; Ra Is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyciylalkenyi, -Rs-OR8, ~R9-0C(0)-R8, -R9~N(R6)R7, -Rs-C(0)R8, -R9-C{0)0R8, -R9-C{0)N(R6)R7, -R9-N(R6)C(0)0R9, ~R9-N(R6)C(0}R8, -R9-!sl{R6}S(0)iRB (where t is 1 or 2), -R9-S(0),0RB (where t is 1 or 2), -Rs-S(0)pR8 (where p is 0, 1 or 2), and -R3-S(0)iN{R6}R'' (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2i -R10-N(Re)2, -R10-C(O)ORs and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyciyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain,
19. 19. The compound of Claim 18 wherein: R1, R4 and R5 are each Independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyi, ~R9b~OR8b, -R9b-C(Q)OR8b, ~R9b~N(R6b)R7b and ~R9b~C(G)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2bis selected from the group consisting of-C{0}R8, hydrogen and alkyl; R2* is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocvciyl, optionally substituted heteroeyelylalkenyi, -R9-GR®, ~R8-GC(0)-R®, ~R9-N(R6)R7, -R9-C(0)R®, -R9-C(0)0R®, -R9~C(G)N(R6)R7, -Rs-N(R6)C{0)0R8, -R9~N(Re)C(0)R8, -R9-N{R6)S(0),R8 (where t Is 1 or 2), -R9-S(G)tOR8 (where t is 1 or 2), ~Rs-S(G)pR8 (where p is 0, 1 or 2), and -R9-S{0)tN{R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cyeioalkyl, optionally substituted cycloalkylaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryi, optionally substituted heteroarvlalkyi, ~R1u-OR®, -R10-CN, ~R,0-NG2f ~R10~N(R8)2, -R10-C(O)QR8 and ~R1G~C(0)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroary! or an optionally substituted W-heterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyl, optionaily substituted heterocyclyl, optionally substituted heterocyclyialkyl, optionally substituted heteroaryi, and optionally substituted heteroaryiaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionaily substituted straight or branched aikylene chain; and each R10 Is an optionally substituted straight or branched aikylene chain.
20. 20. The compound of Claim 18 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, ~R9b-QR8b, ~R9b--C(G)GR8b, -R9b-N(R6b)R7b and -R9b-C{0}N(R6b)R?b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each Rab is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is an optionally substituted non-bridged cycioaikyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocydyi, optionally substituted heterocyciylaikenyl, -R9~OR8, -R9-0C(0)~R8, -Re-N(Re)R7, -R9~C(Q)R8, ~R9-C(Q)GR8, -R9-C(G)N{R6)R7, -R9-N{Rs)C{0)OR8, -R9-N(R6)C(0)R8, -R9-N(R°)S(0)jR8 (where t is 1 or 2), -R9-S(0}t0Rs (where t is 1 or 2), -R9-S(Q)PR8 (where p is 0, 1 or 2), and -R9“S(Q)iN(R®)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocydyi, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NQ2, -R1g-N(R8)2, -R10-C{O)QR8 and -R10-G(O)N(R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted AZ-heterocyclyi; each R“ is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocydyi, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, and optionaiiy substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkyiene chain.
21. 21. The compound of Claim 18 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyi, -R9o-OR8b, ~R9b-C(0)0R8b, ~R9b~N{R6b)R7b and -RSb-C(0)N{R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, aryl and aralkyl, and each R* is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R2ois an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryf, where the monocyclic ary! and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclyialkenyl, -R9-GR8, -R9-GC(Q)-R0, -R9-N(R6)R7, -R9-C{0)R8, -R9-C{G)QR8, -R9-C(0)N(R8)R7, -R9~N(R6)C(Q)0R8, -R9~N(R6)C(0)R8, -R9-N{R6)S(0)tR8 (where t is 1 or 2), -R®-S(0),0R8 {where t is 1 or 2), ~R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloaikyl, optionally substituted cycioalkyiaikyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroaryialkyi, ”R10-OR8. -R10-CN, -R1g-N02, -R10-N(R8)2i -R10~C(O)GRs and -R10-C(G)N(R8)2, or any Re and R'', together with the common nitrogen to which they are both attached, form an optionally substituted tV-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioalkyiaikyi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionaiiy substituted straight or branched aikylene chain.
22. 22. The compound of Claim 21 wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2t is selected from the group consisting of hydrogen, haio, haloalkyi, -R9b~QR8b, -R9b-C(0)0R8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each Reb, R7b and RSb is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2cis optionaiiy substituted bicyclo[2.2.1]heptanyi; RZk is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic ary! and a monocyclic heteroaryl, where the monocyclic aryi and the monocyciic heteroaryl are each optionaiiy substituted by one or more substituents selected from the group consisting of halo, haloalkyi, alkyl, optionaiiy substituted aryl, optionaiiy substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclyiaikenyl, -R9-GRS, -R9-GG{0)-R8, -R9-N(RS)R7, -R9-C(0}Rs, -R9-C{0}0Ra, -R9~C(0)N(R6)R\ -Rs-N(R6)C{0)0R8, -R9-N(R8)C{0)Rs, -R9-N(R6)S(Q)iR8 (where t is 1 or 2), -R9~S(0)t0R8 (where t is 1 or 2), ~Rs-S(0)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyalkyl, optionally substituted aryi, optionally substituted aralkyl, optionally substituted cycloaikyi, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyl, ~R10-QR8, -R!0~CN, ~R10~NO2, -R10-!M(R8}2, -R10-C(O)GR8 and ~R10-C(O)N(R8)2) or any R6 and R', together with the common nitrogen to which they are both attached, form an optionaiiy substituted A/-heteroaryi or an optionaiiy substituted /V-heterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heteroeyclyialkyl, optionally substituted heteroaryl, and optionally substituted beferoarvlalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R1u is an optionaliy substituted straight or branched alkyiene chain.
23. 23. The compound of Claim 22 selected from the group consisting of: W3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-y!)phenyl)-1-{pyridin-2-yi)-1H-1,2,4- triazQle-S.S-diamine; 1-{6~phenyipyridazin~3-y!)~,\f3-{3-fluQro-4-(4-C(1S\2S,4R)~bicye!o[2,2.1jjhepfan~2~ yl)piperazin-1-y!)pheny!)-1/-f1,2,4-triazoie-3,5-diamine; and 1-(4-phenylpyridin-2-yl)-W,-(3-fluoro-4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1- y!)pheny! )-1 H-1,2,4-triazole-3,5-diamine.
24. 24. The compound of Claim 17 wherein: R1, R4 and Rb are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalky!, -R9o-GR8b, -R9i3-C(0)GR8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and RSb is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of s direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of ~C{0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R's is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryi, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyl, alkyl, optionally substituted aryl, optionaliy substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclvlalkenyl, -R®-OR6, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(Q)R8, -R9-C(G)OR8, -R9-C(0)N(R6)R7, -Rb-N(R6)C(0)0R8, -R9~N(R6)C(G)R8, -R9”N{R6)S{0}tR8 (where t is 1 or 2), ”R9-S(0)t0R8 (where t is 1 or 2), -R9-S{0)PR8 (where p is 0, 1 or 2), and -R9-S{0)tN(R6}R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyiaSkyl, optionally optionally substituted heterocyclyl, optionaiiy substituted heterocyclyialkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-GR8, -R10-CW, -R10-NO2, -R10-N(R8)2, -R10-C{O)QR8 and ~R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionaiiy substituted A/-heteroaryl or an optionaiiy substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionaiiy substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioalkylaikyl, optionaiiy substituted heterocyclyl, optionally substituted heterocyclyialkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.
25. 25. The compound of Claim 24 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-QR8b, -R9b~C(G)GR8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each Res, RTb and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2c is selected from the group consisting of ~C(0)R8, hydrogen and alky!; R2k is selected from the group consisting of hydrogen and alkyl; RJ is selected from the group consisting of a bicyclic ary! and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionaiiy substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyciylalkenyl, -RCJ-GR8, -R9-GC(G)-R8, -R9-N(Rs)R7, -R0-C(Q)R8, -R9-C(Q)0R8, -R®-C{0)N(R6)R7, -R9-N(R6)C(0)0R8, -Rs-N(R6)C(0)R8, "R9-N{Rs)S(0))R8 (where t is 1 or 2), -R^Si'C^QR8 (where t is 1 or 2), -Ra-S(Q)PR8 (where p is 0, 1 or 2), and -Rs-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2i -R10-N(R8)2i -R10-C(Q)OR8 and -R'i0-C(O)N{R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted Af-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycioaikyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, and optionally substituted heteroarylalkyl; each R9 is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionaiiy substituted straight or branched alkylene chain,
26. 26. The compound of Claim 25 selected from the group consisting of: 1-(isoquinolin-1-yl)-A/3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-1I2>4-tria20le-3,5-diamine; 1-(6-chloroquinazolin-4-yl)-/V3-(4-(4-methylpiperazin-1-yl)phenyl)-1f/-1,2,4-triazole-3I5- diamine; 1-(4-(4-(5-amino-1-(isoquinolirs-1-yl)-1H-1,2!4-triazo!-3-ylamino}pheny!)piperazin-1- y!)ethanone; W3~{3-fluorQ~4-i4-methylpiperazin-1-yl)phenyl)-1-(isaquino!in-1-yl)-1/-/-1,2,4-triazole-3,5~ diamine; 1-(6,7~dimethoxyquinazoiin-4-y!)-/V3-(3-fluoro-4-(4-methyipiperazin-1-y!)phenyi)-1H-1,2,4-triazole-3,5-diamine; 1 -.(4-( 4-{5-aminO"1 -{6,7-dimethQxyquinazoiin~4~yl)~1 H-1,2,4-triazol-3-ylamino)phenyl)piperazin-1-yl)ethanone; 5-(5-amino-3-(3-fluoro-4-(4-rnethylpiperazin-1-yl)phenylamino)-1H-1,2,4-triazol-1-yl)-1,6- naphthyridin-2(1 H)~one; 4"(5-amlno-3"(3“fluorO“4-(4-methylpiperazin-1-yl)pheny!amino)"1H~1,2,4-iriazol-1- yl)quinazoline-6,7-diol; 4- (5-amino-3-(3-fluoro-4-(4-methy!piperazin-1-yl)phenylamino)-1H-1,2l4-triazol-1-yl)-6- methoxyquinazolin-7-ol; /V3-(4-chloro-3-(4-ethylpiperazin-1 -yl)phenyl)-1 -(6,7-dimethoxyqiiinazoIin-4~yi)-1 H-1,2,4-triazole-3,5-diamine; 1-(4-{5-(5-amino-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1,2,4-triazol-3-ylamino)-2- chloropheny!)piperazin-1-yl}ethanone; 5- (5-amino-1-(6,7-dimethoxyquinazolin-4-yl)-1/7-1,2l4-triazol-3-yIamino)-2-(4- meihylpiperazin-1 -yl)benzamide; and 1 -(6,7-dimethoxyquinazolin-2-yl)-A/3-(4-(4-methylpiperazin-1 -yl)pheny!)-1 /-/-1,2,4-triazole- 3,5-diamine.
27. 27. The compound of Claim 24 wherein: R1, R4 and Rs are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-GR8°, -R9b-C(0)QR8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b Is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9d is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R2c is an optionally substituted non-bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroarvl, where the bicyclic aryl and the bicyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyi, optionally substituted heterocyclylalkenyl, -R9~QR8, -R9-0C(0)~R8, -Rs-N(Re)R7, -R9-C(G)R8, -Rs~C(0)0R8, -R9-C(0)N(Rb)R7, -R9-N(R6)C(0)0R8, -Rs-N(Rs)C(0)R8, -R9-N{R6)S(0)tR8 (where t is 1 or 2), -R9-S(0},0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and ~R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independentiy selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloaikylalkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyclyialkyl, optionally substituted heteroaryl, optionally substituted heteroaryiaikyl, -Rl0-OR°, -R10-CN, -R10-NO2, -R1q~N{R8)2, ~R10~C(O)OR® and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted AZ-heteroaryl or an optionally substituted /V-heterocyclyl; each R® is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikynyl, optionally substituted cycioalkyl, optionally substituted cycloaikylalkyi, optionally substituted heterocyclyl, optionally substituted heterocyclyialkyl, optionally substituted heteroaryi, and optionally substituted heteroaryiaikyl; each R9 Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.
28. 28. The compound of Claim 27 selected from the group consisting of: W5-(4-(4~cyc!ohexy!piperaz!n-1-yl)phenyl )-1 -(8,7-dimethoxyquinazolin-4-yl )-1 HA, 2,4-triazole-3,5-diamine; /^-( 4-(4~(bicycio[3.2,0jheptan-6-yi)piperazin-1-y!)pheny!)-1-(6,7-dimethoxyquinazolin-4-yl)-1 /-/-1,2,4-triazole-3,5-diamine; /V3-(4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(isoquinolin-1-yl)-1H-1,2,4-triazo!e-3,5-diamine; 4-(5-amino-3-(4-(4-cyclohexylpiperazin-1-yl)phenylamino)-1H-1,2,4-triazol-1-yl)-6- methoxyquinazoiin-7-ol; /V3-(4-(4-cyclohexylpiperazin-1-yl)-3-fluorophenyl )-1-(isoquinolin-1-yl )-1//-1,2,4-triazole- 3.5- diamine; //3-(3-chloro-4-(4-cyclohexylpiperazin-1-yl)phenyl)-1-(isoquinolin-1-yi )-1//-1,2,4-triazole- 3.5- diamine; 4-(5-amino-3-(4-(4-cycloheptyipiperazin-1 -yl)phenylamino)-1 //-1,2,4-triazol-1 -yl )-6-melhoxyq u i nazoli n-7-ol; A/3-(4-(4-cydohepiy!piperaz!n-1-y!)pheny!)-1-(6,7“dimethoxyquinazonn"4-yl)--1H-1)2,4-triazole-3,5-diamine; A/3-(4-(4-cycl00ctylpiperazin-1-yl)phenyl)-1-(6,7-dimethoxyquinazolin-4-yl)-1W-1,2,4- triazole-3,5-diamine; A/3-{3-chioro-4-{4-cydohexylpiperazin-1 -yl )ph,eny! )-1 -(8,7-dimethoxyquinazolin-4-yl)-1 W- 1.2.4- triazoie~3,5-diamine; A'3~(4-(4~cyc!o'nexylpiperazin-1 -yi)~3-fluorophenyi )-1 -(6,7-dimethoxyquinazolin~4-yl)-1H- 1.2.4- triazole-3,5-diamine; A/3-{4-(4~cydohepiylp!perazin-1-yi)phenyi)-1-(6!7-dimethoxy!soquirsolin-1-y!)-1H-1,2,4-triazole-3,5-diamine; and 1-(6,7-dimethoxyquinazoiin-2~yl)-A/3-(3-fluoro-4-(4-cyclohsxylpiperaz!n-1-yi}phenyf)-1/Tf- 1.2.4- triazole-3,5-diamine.
29. 29. The compound of Claim 24 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haioaikyi, -R9b-OR8b, -R9b-C(0)0R8b, -R9b-N(R8b)R7b and -R9b-C(0)!4{R8b)R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2cls an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted beterocyciyi, optionally substituted heterocyclyiaikenyl, -R9-GR8, -R9»OC(Q)-R8, -R9-SM(R6}R7, -R9-C(G)R8, -R9-C(0)QR8, -Re-C{0)N(R6)R7, -R9-N(Re)C(0)GR8, -R9-N(R6)C(0)R8, -R9-N(R6}S(0}tRs (where t is 1 or 2), ~R9-S(Q)tOR8 (where t is 1 or 2), -R9-S(0}pR8 (where p is 0, 1 or 2), and -R9-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyi, haloalkyl, hydroxyalky!, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyialkyl, optionally optionally substituted heterocyclyl, optionally substituted heieroeydylaikyl, optionally substituted heteroaryl, optionally substituted heteroaryiaikyi, ~R10-OR8, -R10-C1M, -R10-NO2, -R10-N(Rs)2, -R10-C(O)OR8 and -R10-€{O)N{R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycloalkyialkyl, optionally substituted heterocyclyl, optionally substituted heterocyclvlalkyi, optionally substituted heteroaryl, and optionally substituted heteroaryiaikyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each R10 is an optionally substituted straight or branched alkyiene chain.
30. 30. The compound of Claim 29 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b~QR8b, -Rst,-G{0)0R8b, -R9b-N(R6b)R7b and -R®b-C(0)N(Reb)R7b, where each Rsb, R7b and R8b is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, ary! and aralkyl, and each Rsb is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R2c is selected from the group consisting of optionally substituted bicyc!o[2.2.1]hepfanyi, optionally substituted bicyclo[3.2.0]heptan-6-yl, optionally substituted bicydo[3.3.1]nonanyi and optionally substituted adamantanyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C{0)-'Rs, -R0-N(R6)R7, -R9-C{G)R8, -R9-C(Q)OR8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-R(R6)C(0)R8, -R9-N(R6)S(0)sRa (where t is 1 or 2), -R9-S(G)tGR8 (where t is 1 or 2), -R9-S(0)nR8 (where p is 0, 1 or 2), and -R9-S(G);N{R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryi, optionally substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycioaikylalkyl, optionally optionally substituted heterocyciyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NG2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-G(O)N{R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A?~heierocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, opiionaiiy substituted cycioalkyl, optionally substituted cycloaikyialkyi, optionally substituted heterocyciyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each Ri0 is an optionally substituted straight or branched alkyiene chain.
31. 31. The compound of Claim 30 selected from the group consisting of: 1 -{Ρβηζο[€ί|Μ8Ζθί~2-^)~Μ5-ί4-(4-(5^ο!α[2,2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl)-1 H- 1.2.4- triazole-3,5-diamine; /y5-(4-(4~(bicyc!o[2,2,1 ]heptan-2-yi)piperazin-1-yi)phenyl )-1-(6,7-dimethoxyquinazolin-4-y! )-1 H-1,2,4-triazole-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yi)piperazin-1-yi)phenyl)-1-(isoquino!in-1-yl)-1W“1,2,4-triazole-3,5-diamine; 1-(benzo[d]ihiazol-2-yi)~Af3-(4-(4-(bicycio[2.2.1]heptan-2-y!)piperazin-1-yl)phenyr)-1/7- 1.2.4- triazole-3,5-diamine; /V3-(4-(4-(bicycio[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1-(quinoxalln-2-y!)-1H-1l2,4-triazole-3,5-diamine; /V3-(4-(4-(bicycio[2,2.1 ]heptan-2-yl)piperazin-1 -yl)phenyl )-1 -(6,7-dimethoxyquinazolin-4-y!)-1 Η-1,2,4-triazole-3,5-diamine; /V3-{4-(4-{bicydo[2,2,1]heptan-2-yi)piperazin-1-yi)phenyl)-1-(2-chioro-7-methy!lhieno[3,2-cfj pyrim id in-4-yi)~ 1H-1 .Z^-triazole-S^-diamine; /^-(4-(4-(b!cyc!o[2.2,1]heptan-2-yi)p!perazin~1-yl)phenyl)-1-(2-chloro-6i7-dlmethoxyquinazolin-4-yi)~1 H- 1,2!4-triazoie-3>5~dsamine; 4"{5"aminO“3”(4-(4-{bicydo[2,2.1]heptan-2“yl)piperazin-1-yl)phenyiamino)”1/-/-1,2,4-triazoi-1-yi}"2-chioro-6“methoxyquinazoiin"7-oi; A/3-{4-(4-(bicyclo[2,2,1 ]heptan-2-yi)piperazin-1 -yl)phenyl)-1 -(6-chiQroquinazGiin-4-y!)-1 H- 1.2.4- triazoie-3,5-diamine; 4-{5“aminO“3-(4“{4-(bicydo[2.2.1]heptan~2“yl)piperaz!n-1-yl)-3“fluoropheny!amino)-1H- 1.2.4- iriazoM -yl)“6-methoxyquinazolin-7-ol; N3^ 4-{4-adamantan-2-y!)piperazin-1 -yi)phenyi)-1 -(6,7-dimethoxy~quinazolin-4-y! )-1 H-1,2,4~triazQle-3,5~d famine; A/3-{4-(4-(bicyclo[3.3.1 ]nonan-9-y!)pip8razin-1 -yS)pheny!}-1 -(6 J-dimethoxyqiiinazolin-4·· y!)-1 H-1,2,4-triazoie-3,5-diamine; A/3-{4-(4-(bicydo[2.2.1]heptan"2-yi)piperazin-1-yi)-3-f!uoropheny!)-1-(6,7-dimethoxyqiiinazoiin-4-yi)-1 H-1,2,4-triazo!e-3,5-diamine; A/3-{4-(4-(bicydo[2.2.1]heptan-2-yi)p!perazin-1-yi)phenyi)-1-(6,7-dimeihoxyisGquinoiin-1-y!)-1 H-1,2,4-triazoie-3,5-diamine; A/3-{4-(4-(bicycio[2.2.1]hepian-2-yi)piperazin"1-yi)phenyl)"1-(ihieno[2,3-d]pyrimidin-4-y!)-1 Η-1 ,2,44^2018-3,5-diamine; A/3-(4-(4-(bicydo[2.2.1 ]heptan-2-y!)piperazin-1 -yl)phenyl)-1 -(ihieno[3,2-d]pyrimidin-4-y!)-1 H-1,2,44riazQ!e-3,5-diamin8; ,'V3-{4-(4-(bicydo[2,2.1]heptan-2-y!)piperaz!n-1-yl)phenyi)-1-(6-phenyith!8no[3(2-ifjpyrirnidin-4~yi)-1 H-1,2,4-triazoie-3,5-diamine; /V3-{4~(4-(b!cydo[2,2.1]hepian-2~yl)piperazin-1~yl)phenyi}-2~(8-phenyith!8rfo[2,3-d]pyrimidin-4~yl)-2H-1,2,4-triazGle-3,5-diamine; A/3-(4-(4-(b!cyclo[2,2.1]beptan-2-yl)piperazin-1-y])phenyi}-1-(furo[3,2-c]pyridin-4-yi)-1H-1,2,44riazol8-3,5-diamine; A/3-(4-(4-(bicydo[2.2.1]beptan-2-y!}piperazin-1-yl}phenyi)-1-(6-fiuoroquinazoi!n-4-yi)-1H- 1.2.4- iriazoie-3,5-diamine; iV3-(4-(1-(bicydQ[2,2.1]heptan-2-y])piperidin-4-yl)phenyl)-1-{2-chloro-7”methyithieno[3,2” c/jpyrfmidin-4-yl)-1 H-1,2,4-triazoie-3,5-diamine; i'V3-(4-(4~{b!cydo[2,2.1]heptan-2-yl)piperazin-1-y])phenyi)-1-(2-metbyiquinazolin-4-yi)-1f/- 1.2.4- tnazoie-3,5-diamine; /V3-{4“{4"{bicyclo[2.2.1]heptan-2-yl)piperazin-1"yl)phenyl)-1“(2-(triiSuoromethy!)quinazoS!n-4-yl )-1 H-1,2.4-triazole-3,5-diamine; ^-{4~(4-{bicyclo[2.2.1]h6ptan-2-yi)piperazin-1"y!)phenyl)-1-(2A64rimethylthienQ[2,3-cf|pyrimrdin-4-yl)-1 H-1,2,4-triazole-3,5-diamine; /V3.(4-(4.(bicydo[2.2.1]heptan-2-y!)piperazin-1-y!}phenyi)-1-{5,8"dimethy!thleno[2!3” d]pyrirnidin-4-yI}-1 H~ 1 ,2,4-triazole-3,5~diamine; /^-(4-(4-(( 1 S,2S,4R)-bicyclo[2.2.1 ]beptan-2-yi)piperazin-1 -yi)phenyl)-1 -(2-chloro-7-methylthieno[3,2-c/]pyrimidin-4-yl)-1/7-1,2,4-triazo!e-3,5-diamine; /V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-y!)-3-fluoropheny1)-1-(2-chloro-7-methylthieno[3,2-c/]pyrimidin-4-yl )-1 /7-1,2,4-triazo!e-3,5-diamine; /^-(4-(4-((1 R,2R,4S)-bicycio[2.2.1]heptan-2-yl)piperazin-1-yl)pheny!)-1-(2-chloro-7-methylthieno[3,2-cflpyrimidin-4-yl )-1/7~1,2,4-triazole-3,5-diamine; 1-{2-chiorothienQ[3,2-Q0pynmidin-4-yi)-/V3-( 4-(4-((1 S,2S,4R}~bicydo[2.2.1]heptan-2-yi)-piperazin-1 -yi)phenyl)-1 H~ 1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyquinazoIin-2-yl)-A/3-(4-(4-((1S,2Sl4R)-bicydo[2.2.1]heptan-2-yl)-piperazin-1 -yi)pheny!)-1 H-1 s2,4-iriazole-3,5-diamine; 1-(5-(thiophen-2-yl}thieno[2,3-d]pyrimidin-4-yl)-/V3-(4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1 -yi)phenyi)-1 /7-1,2,4-triazole~3,5-diamine; 1-(6-(4-chlorophenyl)ihieno[3l2-d]pyrimidin-4-yl)-A/3-(4-(4-(bicydQ[2,2.1]hepian-2-yi)-piperazin-1 -yi)pbeny!)-1 /7-1,2,·4-triazoie-3,5-diamine; 1-(6-(1,1-dimetbyiethy!)thieno[3,2-d]pyrimidin-4~yl)-/V3-(4-(4-(bicyclo[2.2.1]beptan-2-yl)-piperazin-1 -yl)pbenyl)-1 /7-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-c/]pyrimidin-4-yl)- //-(4-(4-((1 S,2S,4/?)-bicydo[2.2.1]bepian-2-yi)-piperazin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(thieno[3,2-a]pyrimidin-4-yi)-A/3-( 4-(4-((1 S,2S,4R)-bicydo[2.2.1]hepian-2-yl)-piperazin~ 1 -yi)phenyi)-1 /7-1 ^^-triazole-S^-diamine; 1-(th!eno[2,3-a]pyrimidin-4-yi)-A/3-(4-(4-((1S!2S,4/?}-bicycio[2.2.1]heptan-2-y!)-piperazin-1 -yi)phenyi)-1 /7-1 ,2,4-triazoie-3,5-diamirie; 1-(5-methylthieno[2,3-£/]pyrimidin-4-yl)-/\/3-(4-(4-((1SI2S,4/?)-bicydo[2.2.1]heptan-2-yl)-piperazin-1 -yi)pbenyi)-1 /7-1,2,4-triazole-3,5-diamine; 1-(7-methy!-2-chlorotbieno[3,2-c/|pyrimidin-4-yi)-W3-(4-(4-((1S,2S,4R)- bicydo[2,2.1]heptan-2-yl)-piperazin-1-yl)phenyl )-1 /7-1,2,4-triazole-3,5-diamine; 1-(7-methyithieno[3!2-c/jpyrimidin-4-yi)-A/3-(3-fiuoro-4-(4-(bicycio[2.2.1]bepian-2-y]}-piperazin-1 -yl)pheny!)~1 /7-1,2,4-triazole-3,5-diamine; 1-(thieno[3!2~dlpyrimidin-4-yi}-A/3-(3-fiuoro-4-(4-(bicycio[2.2.1]bepian-2-yiVpiperazin-1-vf)pheny!)-1 Η-1 ^^-triazoie-S.S-diarriirie; 1-(ih!eno[2,3-d]pyrimidin-4-y!)-W3-(3-fluorQ-4-(4-{biGydo[2.2.1]heptan-2-y!}-piperazin“1“ y!)pheny!)-1 H-1,2,4-triazoie~3,5-diamine; 1-(6-fluoroqu!nazoiin-4-y!)-A/3~{3-f!uoro~4-{4~{bicyc!o[2,2.1]heptan-2-yl)-piperazin-1-yl)pheny!)-1 H-1,2,4-triazole-3,5-diamine; 1-(4~methylthieno[3,2-c^yridazin-7-yl )-/^-(4-( 4-(bicydc[2.2.1 ]heptan-2-yl)-piperazin-1- vi)phenyl)-1 H-1 ,2,4-iriazole-3,5-diamine; 1-(7-methy1th!eno[3,2-Q,]pyrimidin-4-yl)-A/3-{3-rτΊΘthyl·4-{4~(bicycio[2.2.1]hepίan-2-yΐ)-piperazin-1 -yl)phenyl )-1 /-/-1,2,44032018-3,5-diamine; 1-(7-methyl·2-chloroίhieno[3,2-d]pyrimidin-4-yί)-A/3~(2-methyi-4-(4-(b!cydo[2.2.1]heptan- 2-yl)-piperazin-1-yl)pbenyi )-1/7-1,2,4-triazoie-3,5-diamine; 1-(7-methyfthleno[3,2-d]pyrlmid!n-4“y])-A/3-(3-f!uoro-4-(4-((1S,2S,4RV bicyd0[2,2.1]heptan-2-yi)-p!peraz!n-1-yl)phenyi}-1/7~1,2,4-triazoie-3,5~diamine; 1-(7-methylthieno[3,2-d]pyrlmidin-4-y!)-W3-(2-methyi-4-(4-{bicydo[2.2,1]heptan-2-y!)-piperazin-1 -yl)phenyl)-1 /7-1,2,4-triazoie-3,5-diamine; 1-(4-meihyIth!eno[3,2-d]pyndazin-7-y!)-/73-(3-f!uoro-4-(4-(bicydo[2.2,1]hepian-2-yi)·· piperazin-1 -yl)phenyl)-1 /7-1,2,44riazoie-3,5-diamine; 1-(4-methyIthleno[3,2-d]pyndazin-7-y!)-/V3-(3-methyi-4-(4-{bicycio[2.2,1lheptan-2-y!)-piperazin-1 -yl)phenyl)-1 /7-1,2,44riazole-3,5-diamine; 1-(7-meίhyl·2-ch!oroίhieπo[3,2·-d]pyrimidίn-4~yi)-Λ/3-{3-·methyί-·4-(4--(bicycIo[2.2.1]heptan- 2-yi)piperazin-1-yl)phenyi)-1H-1,2,44riazoie-3,5-diamine; 1-(4-methylthleno[3,2-d]pyrldazin-7-y!)-/V3-(3-fiuoro-4-(4-({1S!2S,4R)- bicyclo[2.2,1]heptan~2-yi)piperazin~1-yi}phenyi)~1 /7-1,2,44riazoie-3,5-diamine; 1-(2-chioro-6-methoxy-quinoxalin-3-yi)~A/3-(3-fiuoro-4-{4-{(1S,2S,4R)- bicyclo[2.2,1]heptan-2-yi)piperazin-1-yi)phenyi )-1/7-1,2,44riazoie-3,5-diamine; 1-(6,7~d!methoxy-1-methylphthaiazin~4~yl)~A/3-(3-fiuoro-4-(4-{(1S,2S,4R)- bicyclo[2.2,1]heptan~2-yi)piperazin~1-yi)phenyi)-1/7-1,2,44nazoie-3,5-diamine; 1-(4-mefhyithieno[3,2-d]pyridazin-7-yi)-W3~(3-chloro-4~{4-((2S)-bicyc!o[2.2.1]heptan~2-yi)piperazin-1 -yl)pheny!)-1 /7-1,2,44riazoie-3,5-diamine; 1-(4-methyithienot3,2-d3pynda2in-7-yl)-W3-{3-methyl-4-(4-((1S,2SI4R)- bicyclo[2.2,1]heptan-2-yi)p!perazin~1-yi)phenyi )-1/7-1,2,4-triazo!e-3,5-diamine; 1-(7-methyi-2-m-toiyithieno[3,2-d]pyrini!din-4-yi}-/V3-(4~(4-(biGyclo[2.2.1]hepian-2-yi)piperazin-1-yl)phenyi)-1/7-1,2,4-triazoie-3,5-diamine; 1-(7-methyi-2-(3-cyanophsnyl)thieno[3,2-d]pyrimidin-4-yi)-A/3-(4-(4-{bicydo[2.2,1]h8ptan-2-yi)piperazin-1 -yl)phenyi)-1 /7-1,2,4-triazoSe-3,5-diamine; 1-(7-methy!-2-{2-chlorophenyOthieno[3,2-d3pyTimidin-4-yi}-A/3-(4-{4-((2S)“ bicyclo[2.2.1]heptan-2-yl)piperazin~1-yl}phenyl)~1W-1,2,4-triazole-3,5-diamine; 1 -(7-methyl-2-benzo[d][1,3]dioxole -5-ylthieno[3,2-tf|pyrimidin-4-yl)-/V3-(4-(4-((2S)- bicycio[2.2.1]heptan-2-y!)piperazin-1-yi)phenyl)-1H“1,2,·4-triazole-3,5-diamine; 1-(7-methyl-2-pyridin-4-ylthieno[3,2-c^yr!midin-4-yl)-A/3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1 HA ,2,4-triazole-3,5-diamine; 1-(7-methyl-2-(3-(methylsulfonyl)aminophenyl)thieno[3I2-(/|pyrimidin-4-yl 4-((28)-bicyc!o[2.2,1jheptan-2-yl)piperazin-1-yi)phenyl)-1W-1,2,4-triazole-3,5-diamine; l-^-methyl^-CS-ipyrrolidin-l-ylJprop-l-enyOthienofS^-dlpyrimidin^-yl )-^-(4-(4-((25)-bicyc!o[2.2,1]beptan~2-y!)piperazin-1-yl)phenyi )-1/4-1,2,4-triazole-3,5-diamine; 1~(7-methyi-2-(3-(4-m8ihyipiperazin-1~yl)prop-1-eny!)ibienQ[3,2-d]pyrimidin-4-y! 4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1W-1l2,4-triazole-3,5-diamine; 1-(7-methyl-2-(3-(morpholin-4-yl)prop-1-enyl)thieno[3,2-d]pyrimidin-4-yl)-A/3-(4-(4-((2S)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-{7-methyithieno[3,2-d]pyriniidin-4-yl)-W3”(3-ch!oro-4”(4-({1S>2Sl4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyi)-1W-1,2,4-triazoIe-3,5-diamine; l-thienop^-djpyrimidin^-yj-A^-fS-chiorQ^-^-^IS^S^RJ-bicyclop^.lJheplan-i!-yl)piperazin-1 -yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1~thieno[2,3-d]pyrimidin“4-yi-/V3-(3-chioro-4-(4-({1S,2S,4/:?)"bicyclo[2,2.1]hepian-2-yi)piperazin-1-yi)phenyl)-1H-1,2,·4-triazole«3,5-diamine; 1-(7-methylthieno[3,2-c/| pyrimidin~4-yj)~/y3-(3-fiuoro-4-{4-({1S,2S,4/?)- bicycio[2.2.1]heptan-2-yi)piperazin-1-yi)phenyl)-1 /-/-1,214-iriazo!e-3,5-diamine 1“(7-metbyitbieno[3,2-c/|pyrimidin-4-yl)-/*/9-(3-fiuoro-4-{3-(R)-methyl-4- {bicycio[2,2.1]heptan-2-yl)piperazin-1-yi)phenyl)-1W-1,2,·4-trsazo!e-3,5-diamine; 1-(7-methylthieno[3,2-c^yrimidin-4-yl)-/V3-(3-fluoiO-4-(3-(S)-methyl-4- (bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)pheny!)-1W-1,2,4-tri azole-3,5-diamine; 1-(7-nethyltbieno[3,2-d]pyrirnidin-4-yi)-A/3-(3-fluoro-4-(3-(R)-metbyi-4-((1 S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methy!thieRo[3,2~c/jpyrimitiin-4-yi)~/^~(3-f!uoro-4-(3-(S>meihy[-4~((1S\2S\4R)~ bicycio[2.2.1]heptan-2-yi}piperazin-1-yl)pbenyi)-1H-1,2,4-triazoie-3,5-diamiRe; 1-(7-rnethy!thieno[3,2-d3pyrim!din-4-yi}-W3-(3-methyl-4-{4-((1S,2S,4R)- bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(7-methylthieno[3,2-d]pyrim!d!π-4-yi)-Λ/i!~{3-methyi-4~(3-{S)-methyl·4-{(1S,2S,4R)- bicydo[2.2.1]heptan-2-yi)piperazin-1-yi)phenyi)~1H-1,2,4-triazoie-3,5-diamiRe; 1-{7-methylthieno[3,2-£/|pyrinnidin-4-yl)-A/3-(3-methyl-4-(3-(/:?)-methyl-4-((1S,2S,4f?)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 tf-1,2,4-triazole-3,5-diamine; 1-thieno[3l2-£flρyr!m!dfn-4"yl·W3"(3-fίuQro-4“(3-{S)“methyl·4-((1S,2S,4R)" bicyciQi2.2.1]heptan-2-yl)piperazin-1-yl)phenyl )-1 H-1,2,4-triazQie-3,5-diamine; and 1~{2-chlQro-7~methyiihienG[3,2~d]pyrimidin-4-yl)~A/3-(3~melbyi~4-(3~{S)-rnethyi-4- i(1S,2S,4f?)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)phenyl)-1H-1,2,4-triazole- 3,5-diamine.
32. 32. The compound of Claim 17 wherein: R1. R4 and Rs are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b~ORSb, -R9b-C(G)OR8b, -R9b~N(R6b)R7b and -R9b~C(0}M(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9fc is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2cis selected from the group consisting of -C{0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyi; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyciic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyciic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroarvl, optionally substituted heterocyclyl, optionally substituted heteracyclylalkenyl, -R9-OR“, -R9-OC{G)-R8, -Rs-N(R6)R7, -R9-C(G)R8, -R9-G(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)G{0)GRs, -Rs-N(R6)G(G)R8, -R9-N{R6)S(0)[R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R0-S(O)PR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6)R7 (¥/here t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycioalkylaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylaSkyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, ~R1Q~OR8, -R10-CN, -R1Q-N02, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N{R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted /V-heterocyciyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycloelkyiaikyl, optionally substituted heterocyclyl, optionally substituted hetarocyciylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 Is independently seiected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched aikyiene chain.
33. 33, The compound of Claim 32 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, ~R9b~OR8b, ~R9b~C(Q)QRSb, ~R9b~N(R6b)R7b and -RSb-C(Q)N{R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; R2cis selected from the group consisting of-C{0)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is seiected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents seiected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9~OR8, ~R9-0C{0)-R8, -R9-N(R6)R?, -R9-C{0)R8, -R9-C(0)0R8, -Rs-C(0)N(R6)R7, -R9-N(R6)C{0)QR8, -R9-N(R6)C(0)R8, ~R9-N(R6)S{G)tR8 {'where t is 1 or 2), ”R9-S(G)tOR8 (where t is 1 or 2), -R9-S(G)PR8 (where p is 0, 1 or 2), and ”R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, hydroxyaikyl, optionally substituted aryi, optionally substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycloalkyialkyl, optionally optionally substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-GR8, -R10"CN, -R1q~NQ2, -R10~N{Rs)2, -R10-C(O)GR8 and -R10~G(G}N(R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heierocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkyialkyl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched aikyiene chain.
34. 34. The compound of Claim 33 selected from the group consisting of: 1-(5,6-dihydrobenzo[h]quinazo]in-2-yl)-A/3-{4-(4-methylp!pera2:in-1-yl)phenyl)-1/-f-1!2,4- triazole-3,5-diamine; and 1-(5,6-dihydrobenzG[b]cinnQlin-3“yl)“^4-(4-methylpiperazin-1-yi)pheny!)~1H-1,2,4-tRazoie-3,5-diamine.
35. 35. The compound of Claim 32 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R20 is selected from the group consisting of hydrogen, halo, haloaikyl, ~R9b~OR8b, -R9b-C(Q)GR8b, -R9b-N(R6b)R7b and ~R9b~C(Q)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, aikyi, haloaikyl, aryi and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; R2cis an optionally substituted non-bridged cycloalkyi; Rzk is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryi and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyi, alkyl, optionally substituted aryi, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclyialkenyl, ~R9-OR8, -R9-OC(Q)~R0, -R9-N(R6)R7s -R9-C{0)R8, -R9-C(0)0R8, ~R9~C{0)N(R6)R7, -R9~N{R6)C(0)0R8, -R9-N(R6)C{Q)R8, -R9-N(R6}S(0}tR8 (where t is 1 or 2), -R9-S(Q)tOR8 (where t is 1 or 2), ~R9-S(0)pR8 (where p is 0, 1 or 2), and -R9~S(0)tN(R6}R7 (where I is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, aikyi, haioaikyi, hydroxyalkyl, optionally substituted aryi, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloaikylaikyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, optionally substituted heteroaryiaikyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)QRs and -R10-C(O)N(R8)2, or any Re and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyciyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycloaikylaikyi, optionally substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaryiaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain,
36. 36. The compound of Claim 35 selected from the group consisting of: /yT(4„{4-cyciohexylpiperazin-1 -yi)phenyi )-1-(5,6-dihydrobenzo[ft]quinazo!in-2-yl)-1W- 1,2,4-triazoie-3,5-diamine; /^.(^(^cyclohexyipiperazin-l -yl)phenyi)-1 -(5,6-dihydrobenzc[/7]cinnolin-3-yl)-1 HA ,2,4- triszole-3,5-diamine; and 1-(phenanthridin-6-yl)-A/3-(3-fluoro-4-(4-cyclopentylpiperazin-1-yl)phenyl)-1/-/-1,2,4-triazole-3,5-diamine.
37. 37. The compound of Claim 32 wherein: R\ R4 and Rb are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haioalkyl, -Rsb-OR8b, ~R9b-C(Q)ORab, -RSb~N(R6b)R7b and -R9b-C(G)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R2cis an optionally substituted bridged cycioalkyi; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryi are each optionaliy substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionaliy substituted heierocyciyi, optionally substituted heterocyclylalkenyl, -R9-GR8, -R9-0C{0)-R8, -R9-N(Re)R7, -R9-C(0}R8, -Ra-C(0)GR8, R9-C{0)N(R6)R7, -R9-N(R6)C(0)QR8, -R9-N(R6)C(0)Rs, -R9-N(Rs)S(0)tR8 (where t is 1 or 2), -R9-S(Q)tQR8 (where t is 1 or 2), -R9-S(0)PR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycioaikylalkyl, optionally optionally substituted heierocyciyi, optionally substituted heterocyclylalkyl, optionaliy substituted heteroaryl, optionally substituted heteroaryialkyl, -R10-ORS, -R10-CN, -R,0~NG2> -R10-N(R8)2i -R1d-C(G)OR8 and -R10-C{O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryi or an optionaliy substituted A/-heterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, optionally substituted aryl, optionaliy substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioaikylalkyl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryi, and optionally substituted heteroaryialkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

    33. The compound of Claim 37 wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(0)GR8b, -R9b-N{R6b)R7b and -Rsb-C(0)N{Reb)R7b, where each Reb, R7b and RSb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionaily substituted straight or branched aikyiene chain; R2cis optionally substituted bicycio[2.2.1]heptanyl; R2k is selected from the group consisting of hydrogen and aikyi; RJ is selected from the group consisting of a tricyclic aryl and a tricyclic heferoaryl, where the tricyclic aryl and the tricyclic heteroarvi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, aikyi, optionally substituted aryl, optionally substituted heteroaryf, optionally substituted heterocyciyl, optionally substituted heterocyclyiaikenyl, ~R9-QR8, -R9-0C{0)-R8, -R9-N{R6)R\ -R9-C(0)R8, -R9-C(0)0R8, ~R9-C(O)N(R6}R7, -R9-N(R6)C(G)GR8, -R9-N(R8)C(0)R8, -R9-N(Re)S(Q)tR8 (where i is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(Q)PR8 (where p is 0, 1 or 2), and -R9-S(0)iN(R6)R7 (where t is 1 or 2); each R6 and R' is independently selected from the group consisting of hydrogen, alky!, haloalkyl, hydroxyaikyl, optionally substituted aryl, optionaily substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyiaikyl, optionally optionally substituted heterocyciyl, optionally substituted heterocyclyialkyi, optionally substituted heteroaryl, optionally substituted heteroarvlalkyl, -R10-GR8, -R10-CN, -R10-NG2, -Ri0-N{R8}2, -R10-C(O)ORe and -R10-C(G)N(R6)2, or any R6 and R', together with the common nitrogen to which they are both attached, form an optionaliy substituted W-heteroaryl or an optional!'/ substituted W~heterocyc!yl; each Rs is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkyiaikyl, optionaily substituted heterocyciyl, optionaliy substituted heterocyclyialkyi, optionally substituted heteroaryl, and optionally substituted heteroarylaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.
38. 39. The compound of Claim 38 selected from the group consisting of; A/3-{4~(4-{bicyclo[2.2.1]heptan-2~yl)piperazin-1~yl)phenyl)-1-(6,7~dihydro~5H- cyclopenta[4,5]thieno[2,3-c/]pyrirnidin-4-yl)-1 H-1,2,4-triazoie-3,5-diamine; and 1-(pyrido[2l3-b3pyrimidoi4,5~d]thiophene~4-yl)~/V3-(4-(4-(bicycSo[2.2.1]heptan~2-yi)~ piperazin-1-yl)phenyl)-1W-1,2,4-triazole-3,5-diamine.
39. 40. The compound of Claim 2 having the following formula (Ia3):

    wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(G)R8 and -C(0)N{R6)R7; R2e is selected from the group consisting of halo, -OR8, -C(0)R8, -Q(0)0R8, -R1Qe-N(R6)R7, -R10e-C(O)N{R6)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R1(le is an optionally substituted straight or branched aikylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of aryi and heteroaryl, where the aryl and the heteroary! are each optionally substituted by one or more substituents selected from tho group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalky!, cycioaikyiaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyciylaikyi, optionally substituted heterocyclyialkenyl, -R9-OR8, -Rs-O-R'i0-QRs, -r9-o-r10-o-r10-or8, -r9-o-r10-cn, -R9~G~R10~C(Q)OR8, -R9-O-R10-C(O)N(R6)R7, -R9"O-R10-S(O)pR8 (where p Is 0, 1 or 2), -R9-O-R10-N(Rs)R7, -R9-O-R10-C(NR11)N(R11)H, -R9~0C(0}-R8, -R9-N{R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C{0)N(R6)R7, -R9-N{R6)G(0)0R8, -R9~N(R6)C(G)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R®-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(G),N{R6)R7 (where t is 1 or 2); each R6 and R? are each independently selected from the group consisting of hydrogen, alkyl, aikenyi, alkynyl, haioaikyl, haioalkenyi, haloalkynyl, hydroxyaikyi, optionaiiy substituted aryl, optionaiiy substituted aralkyl, optionaiiy substituted araikenyl, optionaiiy substituted araikynyi, optionally substituted cycloalkyl, optionaiiy substituted cyeloalkylalkyl, optionally substituted cycioaikylalkenyi, optionaiiy substituted cycloalkylalkynyl, optionaiiy substituted heterocyclyi, optionally substituted heterocyclyiaikyi, optionally substituted heterocyclylalkenyl, optionally substituted heterocyciylaikynyl, optionaiiy substituted heteroaryl, optionally substituted heteroaryialkyl, optionally substituted heteroarylalkenyl, optionaiiy substituted heteroarylalkynyl, ~R10~OR8, -R10-CN, -R10~NO2, -R10-N(R8)2, -R10~C(O)OR8 and -RIQ”C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionaiiy substituted /V-heteroary! or an optionaiiy substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haioaikyl, haioalkenyi, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyl, optionally substituted araikynyi, optionally substituted cycioalkyl, optionally substituted cyeloalkylalkyl, optionally substituted cycioaikylalkenyi, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyi, optionally substituted heterocyclyiaikyi, optionally substituted heterocyclylalkenyl, optionally substituted heterocyciylaikynyl, optionaiiy substituted heteroaryl, optionally substituted heteroarylaikyl, optionaiiy substituted heteroarylalkenyl, optionally substituted heteroaryialkynyi; each R® is independently selected from the group consisting of a direct bond or an optionally substituted straight or branched alkylene chain; each R10 is an optionally substituted straight or branched alkylene chain; and each K11 is hydrogen, alkyi, cyano, nitro or-OR8.
40. 41. The compound of Claim 40 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2e is selected from the group consisting of halo, -OR8, -C(0)R8, ~C{Q)QR8, -R'0e-N(Re)R7, -R1°8-C(0)N{R6)R7, optionally substituted heterocyciyl and optionally substituted heteroaryl, where each R10a is an optionally substituted straight or branched aikylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroary! are each optionally substituted by one or more substituents selected from the group consisting of halo, haloaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heferocyclyl, optionally substituted heterocyclyialkenyl, -R9-OR8, ~Rs-GC(0)-R°, -R9~N(RS)R7, -R9~C(Q)R8, -R9~C(G)QR8, -Rs~C(0)N(Re)R7, -R8~N(R6)C(0)0R8, -R9-N(R6)C(G)R8, -R9~N(R6)S(G)tR8 (where t is 1 or 2.), -R9-S(0}t0R8 (where t is 1 or 2), -R9-S(0)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R8)R7 (where i is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alky!, haloaikyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaikyl, optionally substituted cycloalkylaikyl, optionally optionaliy substituted heterocyciyl, optionaiiy substituted heterocyclylalkyl, optionally substituted heteroaryi, optionaiiy substituted heteroaryiaikyi, -R1u-GR8, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionaiiy substituted W-heteroaryl or an optionaiiy substituted W-heterocyclyl; each Rs is independently selected from the group consisting of hydrogen, aikyi, haloalkyi, optionally substituted aryl, optionally substituted araikvl, optionally substituted aralkynyl, optionally substituted cycioaikyl, optionally substituted cycloalkylaikyl, optionally substituted heterocyciyl, optionaiiy substituted heterocyclylalkyl, optionally substituted heteroaryi, and optionally substituted heteroaryiaikyi; each R9 is independently selected from the group consisting of a direct bond and an optionaiiy substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.
41. 42, The compound of Claim 41 selected from the group consisting of; 1 -{4-isopropyiphenyi)-Af3-(4-morphoiinophenyi)"1 H-1,2,4-triazole-3,5-diamine; /V3-(4-methoxyphenyi )-1-{pyridin-2-yl)-1H-1,2,4~triazoie-3,5-diamine; ethyl 4-(5-amino-1-(2-chloropyridin-4-yi)-1H-1I2,4-triazol-3-ylamino)benzoate; fSj-ethy! 4-(5-amino-1-(2-(2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)pyridin-4-yl)-1W-1,2,4-triazol-3-ylamino)benzoate; fS)-4-(5-amino-1-(2-(2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)pyridin-4-yl)-1f/-1,2,4-triazol- 3-ylamino)henzoic acid; 1 -(4-(5-amino-1 -(2-fluorophenyi)-1 H-1,2,4~triazol-3-y!amino)phenyl)ethanone; 1-{pyridin-2-yi )-/^-(3,4,5-trimeihoxypheny! )-1,4-1,2,4-triazoie-3,5-diamine; 1 -(pyridin-2-yl )-^-(3,4,5-trifluorophenyl )-1 H-1,2,4~triazo!e-3,5-diamine; 3-(5-amino-1-(pyridin-2-yI)-1H-1,2,4-triazol-3-ylamino)phenol; 1-phenyi-N3-(4-{methy!amlnocarbonyl)phenyi)-N5-methy1-1H-1,2,4-triazQle-3,5-diamine; 1 -phenyi-NJ-(4-{ethyioxocarbonyi)phenyl)-N5-methyi-1 H-1,2,4-triazol8-3,5-diamine; 1-{6-phenyipyridazin-3-yl)~i'V3-(3-fiuoro-4~(4-{pyrrolidin-1-yl)piperidin-1-yi)phenyl)-1/-/- 1,2,4-triazoie-3,5-diamine; and 1 -{4~phenylpyridin-2~y!}-/V3-(3~fluoro~4-{4~{pyrroi!din-1 -yi)piperidin-1 -y!)phenyl)-1 H-1,2,4-triazoie-3,5-diamine.
42. 43. The compound of Claim 40 wherein: R1, R4 and R&amp; are each independently selected from the group consisting of hydrogen and aikyl; RZe is selected from the group consisting of halo, -OR8, -C(Q)R8, -C(0)GR3, -R!Qe-N(R6)R7, -R10e-C(O)N(R6)R7, optionally substituted heterocyclyi and optionally substituted heteroaryi, where each R10e is an optionally substituted straight or branched aikylene chain; Rzd and R2f are each independently selected from the group consisting of hydrogen, halo, aikyl and -OR8; RJ is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryi, where the bicyclic aryl and the bicyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionaliy substituted heterocyclyi, optionally substituted heterocyciylalkenyl, -R9~0RS, -R9-0C(0)-R8, -R9-N{R6)R7, -R9-C{0)R8, -R9-C(0)0Rs, -Rs-C(0)N{R6)R7, -R9-N(R6)C(Q)GR8, -R®-N(R6)C(0)R8, -R9-N(R6)S(G)tR8 {where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyaikyl, optionally substituted arvi, optionally substituted aralkyl, optionally substituted cycloaikyi, optionaiiy substituted cycloaikylalkyl, optionally optionally substituted heterocyclyl, optionaiiy substituted heterocyciyialkyl, optionaiiy substituted heteroaryl, optionaiiy substituted heteroarylalkyl, -R10-QR8, -R10-CN, -R10~NO2, -R10-N(R8)2, -R10-C(O)GR8 and -R‘0-C(O)N(R8)2, or any R6 and R', together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted /V-heierocydyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionaiiy substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloaikylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyciyialkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.
43. 44. The compound of Claim 43 selected from the group consisting of: 1-(4-{5-amino-1-(quinoxalin-2-yl)-1H~1,2,4-iriazol-3-yiamino)phenyl)ethanone; 3-(4-( 5-amino-1-(quinoxalin-2-yl )-1 H-1,2,4-triazol-3-ylamino)phenyl )-1-(pyrrolidin-1- yi)propan-1-one; 1 -(6,7-dimethoxyquinazolin-4-y!)-A/3-(4-(1-methylpiperidin-3-yloxy)phenyl)-1/7-1,2,4-triazole-3,5-diamine; 1-(isoquinolin-1-yl)-/V3-(4-(1-methylpiperidin-3-yloxy)phenyl)-1/7-1,2,4-triazole-3,5- diamine; 1-(isoquinolin-1-yl)-/V3-(4-morpholinophenyl)-1H-1,2,4-triazole-3,5-diamine; 1 -(6,7-dimethoxyquinazolin-4-yl)-A/3-(4-morpholinophenyl )-1 HA, 2,4-trlazoie-3,5-diamine; W‘i-(3-chloro-4“morphoiinophenyi)-1-(6,7-dimethoxyquinazolin-4-yl)-1H-1l2,4-friazole-3,5- diamine; W8-(3-chloro-4-morpho!inopheny!)-1 -(6-chloroquinazolin-4-yl)-1 /7-1,2,4-triazoie-3,5-diamine; /^-(S-fluoro-^morpholinophenyiJ-l-Cisoquinolin-l -yl)-1 /-/-1,2,4-tria20le-3,5-diamine; 1 ~(6,7-dimeihoxyquinazoSin-4-yl)-/V3~{3-f!uoro-4~morpho!inophenyl)-1 H-1,2,4-iriazole~3,5~ diamine; 1-(isoquinolin-1-yl)-/V3-(4-((4-methyIpiperazin-1-yl)methyl)phenyl)-1H-1,2,4-triazole-3,5- diamine; H3-{4~((H)~3-{dimeihylamino)pyrrolidsn-1~yi}phenyi)-1-(isGqu!nolin-1~yi)-1H"l2,4-iriazo!e- 3.5- diamine; /^^-((SJ-S-tdimethylaminoJpyrrolidin-l-ylJphenyiJ-l-Cisoquinolin-l-yO-l H-1,2,4-triazole- 3.5- diamine; Hisoquinolin-l-ylWV^-ioxazoi-S-yOphenyl )-1 H-1,2,4-triazole-3,5-diamine; 1 -(isoquinoiin-1-yi )-/^-(4-(1 -methyl piperidin-4-yl)phenyl)-1 H-1,2,4-triazoie-3,5-diamine; 1-(6,7-dimethoxyquinazolin-4-yl )-/^-(4-( 1-methylpiperidin-4-yl)phenyl )-1 H-1,2,4-triazole- 3.5- diamine; 4-(5-amino-3-(4-(1-methylpiperidin-4-yl)phenylamino)-1H-1,2,4-triazol-1-yl)-6- methoxyquinazolin-7-ol; 1-(6,7-dimethoxyquinazolin-4-yl}-/V3-(4-((S)-3-(dimethylamino)pyrrolidin-1-yl)phenyl )-1 H- 1.2.4- ir!azoIe-3,5-diamine; 4-(5-amino-3“(4-{1-methylpiperidin-4-yi}phenylamino)-1H-1,2,4-tr!azo!-1-y!}quinazoiine- 6,7-diol; 1 -(6,7-dimethoxyquinazolin-4-yl)-A/3-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyisoquinolin-1-yl)-/V3-(4-(1-methylpiperidin-4-yl)phenyl)-1H-1,2,4-triazole- 3.5- diamine; 1-(6,7~d!met'noxyquinazoiin~4-y1)~H3-(4~( 4-( cyciopenty!)piperazin-1-yicarbonyi)phenyi}-1 H-1,2,4-triazole~3,5-diamine; 1-(7-methylthieno[3,2-d3pyrimidin-4-yl)-A/3-(4-(4-(cyciQpentyl)piperazin-1-ylcarbonyl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1~(7^θίήγ!~2-οΗΙθΓθίΗ!βηο[3,2-^ργΓ^ϊϋίη-4~γΙ)-,^-(4~({2-·(ργπΌΜ!η~1-yl)ethyl)aminocarbonyl)pbenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(6,7-dimeihoxyquinszolin~4-yi)~H3-(3-fiuoro-4-(4-piperidin-1-y!piperidin-1-yl)pbenyi)-1H- 1.2.4- triazole-3,5-diamine; 1~(7”methyi-2-ch!orotbieno[3,2-djpyrimidin-4-yl}-A/5-(3-fluoro-4-(4-piperidin-1-yipiperidin-1-yl)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(7-methy!-2-chlorothieno[3,2-d]pyriiT(idin-4-yl)-A/3-(3-fluoro-4-(3-diethyiam!nopyrroiidin-1-yi)pbeny! )-1 H-1,2,4-triazoie-3,5-diamine; 1"(7-methyl-2"Chlorothieno[3,2-£/|pyrim!din-4-y1)-/V3-(3-i!uoro-4-{iso!ndo!in-2"yl)phenyl}-1 Η-1,2,4-triazole-3,5-diamine; 1-(6,7-dimethoxyqu!nazolin-4-yl)-W3-{3-fluoro-4-(iso!ndol!n-2-yi)pheny!)-1W-1,2,4-triazoie- 3,5-diamine; 1-(2-chloro-6-methoxy-quincxalin-3-yl)-/V3-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1- y!)phenyl)-1 H-1,2,4-triazole-3,5-diamine; 1-(7-meihy!thieno[3,2-d]pyrim!d!n-4-yi)-/\/3-(3-fluoro-4-{4-(2-azab!cycio[2,2.1]hepian-2~ yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3I5-diamine; 1-(7-methylthieno[3,2-£/]pyrimidin-4-yl)-/V3-(4-(1-(bicyclo[2.2.1]heptan-2-yl)piperidin-4-yl)phenyi)-1/7-1,2,4-triazole-3,5-diamine; and 1~(7-methy!thieno[3,2-d3pyrimid!n-4-y!)-W3~(3-f3uoro4-{1-({1S,2S,4R)~bicyc!o[2.2,1]heptan~ 2-yl)piperidin-4-yl)phenyl)-1 /7-1,2,4-triazole-3,5-diamine.
44. 45. The compound of Ciaim 40 wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and aikyi; RZe is selected from the group consisting of halo, -OR8, -C(0)R°, -C(0)0R8, -R10e-N(R6)R7, -R1Qe-C(0)N(R6)R7, optionally substituted heterocyciy! and optionally substituted heteroaryl, where each R10e is an optionally substituted straight or branched alkyiene chain; RZa and Rzf are each independently selected from the group consisting of hydrogen, halo, aikyi and -OR8; R3 is selected from the group consisting of a tricyciic aryl or a tricyclic heteroaryi, where the tricyclic aryl and the tricyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloaikyl, aikyi, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyciy!, optionally substituted heterocyclylalkenyl, -R9-OR8, ~R9-GC{Q)-R8, -R9-N{R6)R7, -R9-C(Q)R8, -R9-C(G)OR8, -R9-C(G)N(R6)R\ -R9-N{R6)G(0)0Rs, -R8-N(R6)C(0)R3, -R9-N(R6)S(G)tR8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR3 (where p is 0, 1 or 2), and ~R9-S(0).,N(R6)R7 (where t Is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycioaikylaikyl, optionally optionaliy substituted heterocycfyi, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-QR8, -R10-CN, -R10-NG2j ~R10~N(R8)2i ~R10~C(Q)GR8 and ~R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted /V-heterocyciyl; each Rb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyi, optionally substituted heterocycfyi, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
45. 46. The compound of Claim 45 selected from the group consisting of; 1-(5,6-dihydrobenzo|/7]cinnolin-3-y! 3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1- yl)phenyl)-1 H-1,2,4-iriazoie-3,5-diamine; 1“(8-methoxy"5,5-dimethyl--5W-chromeno[4,3-c]pyridazin--3"yl)”A/3"(3-fiuorQ-4"{4(4" methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine; 1-(phenanthridin-6-yi )-/^-(4-(1 -methylpiperidin-4-yi)phenyl )-1 H-1,2,4-triazole-3,5-diamine; and 1"(phenanthridin--6-yi)--i'V3-(3”methy!-4"{4“pyrrol!din“1"ylpiperidin“1-yi)phenyl)-1/-/-1,2,4-triazole-3,5-diamine.
46. 47. The compound of Claim 2 having the following formula (Ia4);

    wherein; R\ R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(Q)RS and -C(0)N(Ra)R7; R2h is selected from the group consisting of hydrogen, -N{R6h)R7h, optionally substituted heferocyclyl and optionally substituted heteroar/i, where R6h is hydrogen or alky! and R7h is an optionally substituted bridged cycloalkyl; R2a is independently selected from the group consisting of hydrogen, halo, -OR8 and -Rs-N(R6)R7; R2', R2' and R2i are each independently selected from the group consisting of hydrogen, halo and -OR8; R8 is selected from the group consisting of aryl and heteroaryi, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haioalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyciylaikenyl, -R9~QR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)QR8, -R9-C(Q)N(R6)R7, -R9-N(R6}C{G)GR8, ~R9-N(R6)C(G)R8, -R9-N(R6)S(G)tR8 (where t is 1 or 2), -Rs~S(G$tOR8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and ~R9-S{G)tN(R6)R7 (where t is 1 or 2): each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyiaikyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyciyialkyi, optionally substituted heteroaryi, optionally substituted heteroarylaikyl, -R10-GR8, -R10~CN, -R10-NO2, -R10-N(R8}2> -R1c,-C(0)0R8 and -R10-C(O)N(R8)2l or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N~heteroaryi or an optionally substituted N-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikynyl, optionally substituted cycioalkyl, optionally substituted cycloalkyiaikyi, optionally substituted heterocyclyl, optionally substituted heterocyciyialkyi, optionally substituted heteroaryi, and optionally substituted heteroarylaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain,
47. 48. The compound of Claim 47, wherein: R1, R4 and RD are each independently selected from the group consisting of hydrogen and alkyl; R2il is selected from the group consisting of hydrogen, -N(R6h)R7h, optionally substituted heterocyciyl and optionally substituted heteroaryl, where R6h is hydrogen or alkyl and R'h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9~N{R6)R7; Rzf, Ra and R2j are each independently selected from the group consisting of hydrogen, halo and -OR8; R·5 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkenyl, -R9~OR8, -R9-0C(0)-R8, ~R9-N{RS)R7, -R9~C(G)R8, -R9~C(G)OR8, -R9-C{0)N(R6)R7, -Rs-N(R6)C(0)0R8, -R9-N(R6)C{G)R8, -R9-N{R6)S(G)}R8 {where t is 1 or 2), -R9~S{0)tGR8 (where t is 1 or 2), -Rs-S(0}PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hvdroxyalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycioaikylalkyi, optionally optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, -R10-QR8, -R10~CN, -R10-NO2, -R10-N(Rs)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted AZ-heterocyelyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioaikylalkyi, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, and optionally substituted heteroarylaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chairs; and each R10 is an optionally substituted straight or branched alkylene chain.
48. 49. The compound of Claim 47, wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of hydrogen, ~N(R6h}R7h, optionally substituted heterocyciyl and optionally substituted heteroaryl, where RSh is hydrogen or alky! and R7h is an optionally substituted bridged cycloalkvl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2f, RZ| and RZi are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a bicydic aryl and a bicyclic heferoaryi, where the bicyclic aryl and the bicyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(Q)R®, -R9-C(0)0R®, -R9-C(0)N{R6)R7, -R9~N(R6)C(G)OR8, ~R9~N(R6)C(Q)R8, -R9-N(R6)S(0)tR® (where t is 1 or 2), -R9-S(G)tOR8 (where t is 1 or 2), -R9-S(0)pR® (where p is 0, 1 or 2), and -R9-S{0)tN(R6)R7 (where t is 1 or 2); each Rn and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycioatkylalkyl, optionally optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, optionally substituted heteroaryiaikyi, -R10-GR8, -R10-CN, ~R10-NO2, -R10-N(R8)2, -R1q-C(0)0R8 and -R10-C(O)N(R8)2, or any Rs and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted /V-beterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloaikyi, optionally substituted cycioalkylalkyi, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, and optionally substituted heteroaryiaikyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each R10 is an optionally substituted straight or branched alkyiene chain.
49. 50. The compound of Claim 49, wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of optionally substituted heterocyclyi and optionally substituted heteroaryi; R2d, R2f, R2s and R2i are each independently hydrogen; R3 is selected from the group consisting of a blcyclic aryl and a bicycllc heteroaryl, where the bicyciic aryl and the bicyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyi, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyi, optionally substituted heterocyclylalkenyi, -R®-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(Q)R8, -R9-C(0)0Rs, -Rs-C(0)N{R6)R7, ~R9-N(R6)C(0)QR8, -R9-N(R6)C(0)R8, -R9~N(R6)S(0)sR8 (where t is 1 or 2), -R9-S(Q)tQR8 (where t is 1 or 2), -R9~S{Q)pR8 (where p is G, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each Ra and R7 is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted eycioalkylalkyl, optionally optionally substituted heterocyclyi, optionally substituted heterocyclylaikyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyi, -R10-OR8, -R10~CN, -R10-NG2, -R10~N(R8)2i -R10-C(Q)QR8 and ~R10-C(Q)N(K8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted Af-heferoaryl or an optionally substituted N-heterocyclyi; each Rs is Independently selected from the group consisting of hydrogen, alkyl, haioaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted eycioalkylalkyl, optionally substituted heterocyclyi, optionally substituted heterocyclylaikyl, optionally substituted heteroaryi, and optionally substituted heteroarylalkyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
50. 51. The compound of Claim 50 selected from the group consisting of: 1-{7~rnetbyl~2-chloroihieno[3,2-cflpyrimidin-4-yl)-/V3-(7-pyrrolidin-1~yl -6,7,8,9-tetrahydro- 5/-/-benzc[7]annulene-2-yl)-1W-1,2,4-triazole-3,5-diamine; and 1-(6,T-dimethoxyquinazolin^-yO-A^-iT-pyrrolidin-l-yl-e,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1 H-1,2,4-triazole-3,5-diamine.
51. 52. The compound of Claim 49, wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is -N(Rbh)R7h where Ron is hydrogen or aikyl and R7h is an optionally substituted bridged cycloaikyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2f, R2! and R2i are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a bicyclic aryl and a blcyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, aikyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclvl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-OC(0)~Rs, -R9-N(R6)R7, -R9-C(0)R8, ~R9»C(Q)OR8, -R9-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R9-N(R6}C(0)R8, -R9-N(Rs)S(Q),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9~S(Q)PR8 (where p is 0, 1 or 2), and -R8-S(0),N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloaikyl, optionally substituted cycloalkylaikyi, optionally optionally substituted heterocyclyi, optionally substituted heterocyciylalkvl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR3, -R10-CN« -R10-NO2, -R10-N(R8)2i -R10-C(O)ORa and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted W-heterocyclyl; each K8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycloa I ky I alkyl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionally substituted heieroaryi, and optionally substituted heteroaryiaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each K10 is an optionally substituted straight or branched alkyiene chain.
52. 53. The compound of Claim 52, wherein: R1, R4 and Ra are each independently selected from the group consisting of hydrogen and alkyl; R2h is -N(R6h)R7h where R5h is hydrogen or alky! and R?h is optionally substituted bicyclo[2.2,1]heptanyl; R2d is independently selected from the group consisting of hydrogen, halo and -OR8; R2f, R2' and RSi are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a bicyclic aryl and a blcyclic heieroaryi, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloaikyl, alkyl, optionally substituted aryl, optionaliy substituted heieroaryi. optionally substituted heterocyciyl, optionaily substituted heterocyclylalkenyl, -Rs-OR8, -R9-0C(0)-R8, -R9~N(Re)R7, -R9-G(G)R8, -R9-C(0)0R8, -Rs-C(0)N(R6)R7, ~R9-N(R6)C(0)0R8, -R9-N{R6)C(0)R8, -R9-N(R6)S{0)sR8 (where t is 1 or 2), -R9-S(0}t0R8 (where t is 1 or 2), -Rs~S(0)pR8 (where p is 0, 1 or 2), and -R0-S(O)tN(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, aikyi, haloaikyl, hydroxyalkyi, optionaliy substituted aryl, optionaliy substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycioaikylalkyl. optionally optionaliy substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionaliy substituted heieroaryi, optionaily substituted heteroaryiaikyl, -R10-OR8, -R10-CN, ~R10~NQ2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(G)N{R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-beieroaryi or an optionaliy substituted iV~heteroeyc!yS; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, optionaily substituted aryl, optionaily substituted aralkyl, optionaily substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally substituted heterocyclyi, optionally substituted heterocyclylaikyi, optionally substituted heteroaryl, and optionally substituted heteroaryialkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; and each R10 is an optionally substituted straight or branched aikyiene chain.
53. 54. The compound of Claim 53 selected from the group consisting of: 1-(7-methyl-2-ch!orothieno[3,2-cf]pyrim!din-4-yl)-Af?-{7-(/y-methyi-/y~b!cyclo[2.2.1]heptan- 2-yl}amino-6,7,8,9-tetrahydro-5H~benzo[7]annulene-2-yi)-1H~1!2!4-triazole-3,5- diamine; 1-(7-methyl-2-chiorothieno[3,2-c/|pyrim!din-4-yl)-W'3-{7-{W-b!cycio[2.2.1]heptan-2- yl)amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5- diamine; 1-(6,7-dimethoxyquinazolin-4-yl )-/^-(7-(/V-bicyclo[2.2.1]heptan-2-yl)amino-6,7,8,9- tetrahydro-5f/~benzo[7]annulene-2~yi}-1 H-1,2,4-triazole-3,5-diamine; and 1-(6,7-dimethoxyquinazolin-4-yl )-/^-(7-(/V-methyl-A/-bicyclo[2.2.1]heptan-2-yl)am!no-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1 W-1,2,4-iriazole-3,5-diamine.
54. 55. The compound of Claim 49 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is hydrogen; R2d is -R9-N(R6)R7; R2f, R2' and R2’ are each independently selected from the group consisting of hydrogen, halo and -ORs; R3 is selected from the group consisting of a bicycllc aryl and a bicyclic heteroaryi, where the bicyclic aryi and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyi, alkyl, optionally substituted aryi, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, ~R9-ORs, -R9-QC(Q)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -Rs~N(R6)C(0)0R8, -R9-N(R6)C(G)R8, -R9-N(R6)S(0)iR8 (where i is 1 or 2), -Rs-S(0)iGR8 (where t is 1 or 2), -Rs-S(0)pR8 (where p is 0, 1 or 2), and -R9-S{0}tN{R6)R7 (where t Is 1 or 2); each R6 and R7 is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocvclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, ~R10-QR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-beteroaryl or an optionally substituted AZ-heterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyl, optionally substituted heterocyclyl, optionally substituted heierocyclyialkyi, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
55. 56. The compound of Claim 55 which is 1-(7-methyl-2-chlorothieno[3,2- c/]pyrimidin-4~yi)-A7,-{8-(2-dietbyiaminGethyl)-9-hydroxy~6,7,S,9~tetrahydra-5H- benzo[7]annulene-2-yl)-1 H-1,2,4-tnazole~3,5-diamine.
56. 57. The compound of Claim 47, wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; KZh Is selected from the group consisting of hydrogen, ~N(R6h}R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where Reh is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; RZd is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2f, R2' and R2) are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-GR8, -R9"QC(Q)-R8; -R9-N(R6)R7, -R9-C{0)R8, -R9-C(Q)OR8, -R9-C(0)N(R8)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)G(0}R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9~S(0),N{R6)R7 (where t is 1 or 2); each R6 and R7 is Independently selected from the group consisting of hydrogen, alkyl, haioaikyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycioalkylalkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyclyiaikyl, optionally substituted heteroaryi, optionally substituted heteroaryialkyl, -R10-OR8, -R10-CN, -R10-NQ2, -R10-N(R8)2i -R10--C(O)GR8 and -R1C-C(0)N(R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, optionally substituted ary!, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioalkylalkyi, optionally substituted heterocyclyl, optionally substituted heterocyclyiaikyl, optionally substituted heteroaryi, and optionally substituted heteroaryialkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkyiene chain,
57. 58. The compound of Claim 1, which is a compound of formula (lb):

    wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; R2 is ary! optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haioalkyi, alkyl, cycioalkyl, eyeioalkyiaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaryialkyi, optionally substituted heteroaryiaikenyi, optionally substituted heterocyciyl, optionally substituted heterocyciylalkyl, optionally substituted heterocyclyialkenyl, -R9-QR8, ~R9~Q~R10~QR8, -R9~O~R10~O-R1q-OR8, -R9-O-R10-CN, -Rs-O-R10-C(O)OR8, -R9~G~R10~C(Q)N(R6)R7, -R9-G-R10~S(Q)oR8 {where p is 0, 1 or 2), -R9~G~R1d~N{R6)R7, -R9-0-R1q~C(NR11)N(R11)H, -R9-OC(Q)-R8, -R9-N(Rs)R7, ~R9~C(Q)R8, -Rs~C(0)0R8, -Rs-C(0)N(R6)R7, ~R9-N(R6)C(Q)QR8, -R9~N(R6)C(G)R8, -R9“N(R6)S(0){Rs (where t is 1 or 2), -R9~S{0)t0R8 (where ΐ is 1 or 2), -R9-S(G)pR8 (where p is 0, 1 or 2), and -R9-S(G).N(R6)R7 (where t is 1 or 2); RJ is selected from the group consisting of aryl and heteroaryl, where the aryl and the heieroaryi are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitre, halo, haioalkyi, alkyl, cycloalkyl, cyoloalkyialkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heieroaryi, optionally substituted heteroaryialkyi, optionally substituted heteroaryiaikenyi, optionally substituted heterocyciyl, optionally substituted heterocyciylalkyl, optionally substituted heterocyclyialkenyl, -R9-OR8, -R9~O-R10~OR8, -R9-G-R10-G-R10-OR8, -R9-O-R10-CN, -R9-Q-R10-C(0)OR8, -R9-G-R10-C(0)N(R6)R7, -R9~O-R10~S(O)pR8 (where p is 0, 1 or 2), -R9-O-R10-N(Rs)R7, -R9-0-R10-C{NR11)N(R11)H, -R9-OC(G)-R8, -R9-N{R6)R7, -R9-C(0}R8, -R9-C(0)GR8, -R9-G(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R^NiR^S^R8 (where t is 1 or 2), -R9-S(0)tGR8 (where t is 1 or 2), -Rs-S{0)sR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6)R7 (where t is 1 or 2); each RD and R7 is independently selected from the group consisting of hydrogen, aikyl, alkenyl, alkynyl, haioalkyi, haloalkenyi, haioaikynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioalkyialkyl, optionally substituted cycioalkyiaikenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyciyl, optionally substituted heterocyciylalkyl, optionally substituted heterocyclylalkenyi, optionally substituted beterocyclyiaikynyi, optionally substituted heteroaryl, optionally substituted heteroarylaikyi, optionally substituted heteroaryiaikenyi, optionally substituted heteroarylalkynyi, -R10-GR8, -R10-CN, -R'iG-N02, -R'°-N(R8)2, -R10-C(G)ORe and ~R10~C(G)N(RB)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted /V-heterocyciyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyi, haloalkyl, baloalkenyl, haloaikynyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyl, optionally substituted aralkynyl, optionally substituted cycloalkyi, optionally substituted cycloaikyiaikyl, optionally substituted cycloalkylalkenyi, optionally substituted cycloalkylaikynyl, optionally substituted heterocvclyi, optionally substituted heterocyclyialkyi, optionally substituted heterocyclylalkenyl, optionally substituted heterocyciyialkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched aikynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched aikynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or -OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.
58. 59. The compound of Claim 58 having the following formula (Ib1):

    wherein: R1, R4 and R° are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(G)RS and -C(Q)N{RS)R7; R2a is -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyciyL and R10a is an optionally substituted straight or branched alkyiene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haioalkyl, aryl, aralkyl, -R"-GR89, -R"-C(0)R89, -R"-C(0)0R8g, -R9g-N(R69)R7g and -R9g-C{G)N(R6g)R7g, where each RSg, R7® and R®9 is Independently selected from the group consisting of hydrogen, alkyl, haioalkyl, aryl and aralkyl, and each R9® is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haioalkyl, alkyl, cycloalkyl, cycloaikylaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyi, optionally substituted heterocyciyl, optionally substituted heterocyclyialkyl, optionally substituted heterocyclylalkeny!, -RS-QR8, ~R9~O~R10~OR8, -R9~O-R10~O-R10~GRa, -R8-O-R!0-CN, ~R8-G~R10-C(O)OR8, ~R8-O~R10-C(O)N(R6}R7, ~R9-O~R10~S(O)pR8 (where p is 0, 1 or 2), -R^G-R^-NiR^R7, -R9-O-R10-C(NR11)N(R11)H, -R9-OC(Q)-K8, -Rs-N(R6)R7, -R9-C(0)R8, -R9~C(G)OR8, -R9-C(0)N(R6)R7, -R9-N(R6)C(G)OR8, -R9-N(R6)C(G)R8, -R9-N(R6)S(0)sR8 (where t is 1 or 2), -R9-S(0)t0Re (where t Is 1 or 2), -R0-S(O)PR8 (where p is 0, 1 or 2), and -R9-S{0),IM{R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haioalkyl, haloalkenyl, haioaikynyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyl, optionally substituted araikynyl, optionally substituted cycloafkyl, optionally substituted cycloaikylaikyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyciyl, optionally substituted heterocyclyialkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyi, optionally substituted heteroarylalkynyl, -R10-QR8, -R10-CN, -R10-NG2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted A/-heterocyclyi; each R° Is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyi, haloalkyl, haioaikenyl, haloalkynyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyi, optionally substituted aralkynyl, optionally substituted cycioalkyl, optionally substituted cycioaikylalkyl, optionally substituted cycloalkylalkenyi, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclvlaikenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyi, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched aikynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched aikynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or -OR8.
59. 60. The compound of Claim 59 wherein: R!, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R108-N(R6a)R73 where Ktaa and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted /V-heterocyclyl, and R10a Is an optionally substituted straight or branched alkylene chain; R20 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R9s-OR8s, -R9s-C(G)R8s, ~R"~C(0)GR89, -R9g-N(R6s)R7g and -R"-C{0)N(R69)R7s, where each R®9, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R" is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; RJ is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic ary! and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from fhe group consisting of halo, haioaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyciyl, optionally substituted heterocyclyialkenyl, -R9~OR8, -R9-0G(0)-R8, -R9-N(R6)R7, -R9-C{G)R8, -R9-C(0)GR8, -R9-C(0)N(R6)R7, -R9-N(R6)C{Q)0R8, -R9-N(R6)C(Q)R8, -R9-N(R0)S{O)sR8 (where t is 1 or 2), ~R9~S(0),0R8 (where t is 1 or 2), ~R9~S(0)pR8 (where p is 0, 1 or 2), and -R9-S(Q)iN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, hydroxyalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloaikyl, optionally substituted cycloalkyialkyl, optionally optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyi, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)2i -R10-C{O)OR8 and ~R10-C{O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionaliy substituted A/-heterocye!yi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloaikyl, optionaliy substituted cycloaikylaikyi, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, and optionaliy substituted heteroarylalkyi; each R9 is independently selected from the group consisting of a direct bond and an optionaliy substituted straight or branched alkylene chain; and each R1G is an optionaliy substituted straight or branched alkylene chain.
60. 61. The compound of Claim 59 wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyi; R2a is -R10a-N(R6a}R7a where RSa and R7a, together with the common nitrogen to which they are both attached, form an optionaliy substituted W-heteroaryl or an optionally substituted W-heterocyclyl, and R103 is an optionally substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloaikyl, aryl, aralkyl, -R"-OR89, -R"-C(G)RSs, -R"-C(0)GRSg, ~R9g-M(R®3)R79 and -R"~C(G)N(R6s)R7a, where each R69, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, aryl and aralkyl, and each R®3 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkvlene chain; R3 is a monocyclic ary! optionally substituted by one or more substituents selected from the group consisting of halo, haloaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-GR8, -RS~QC(Q)~R8, -R9-N{R6)R7, -R9-G(0}R8, -R9-C(G)OR8, -RS-C(G)N(R®)R7, -R9-N{R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S{0)tQR3 {where t is 1 or 2), -Re-S(0)pRe (where p is 0, 1 or 2), and -R9-S(G};N(R6}R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, hydroxyaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaikyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-QR8, -R10-CN, -R10-NO2, -R10»N(R8)2, ~R10~C{O)OR3 and -R10~C{Q)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroary! or an optionally substituted /V-heterocydyl; each Rs is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycioaikyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R® is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
61. 62. The compound of Claim 61, which is 1~phenv!-A/6-(4-(2~(piperidin-1~ yl)ethoxy)phenyl)-1/-/-1,2,4-triazole-3,5-diamine.
62. 63. The compound of Claim 60 wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyi; R2a is -R10a-N(RDa)R7a where Roa and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl, and R1Qa is an optionally substituted straight or branched alkyiene chain; R2s is selected from the group consisting of hydrogen, halo, alkyl, haioalkyi, aryl, aralkyl, "R93~OR89, -R"-C{0)R89, ~R99-C(Q)OR89, -R"-N(R69)R79 and -R"-C(0)N(R6b)R73, where each R®9, R'9 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haioalkyi, aryl and aralkyl, and each RSg is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R® is a monocyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of halo, haioalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryS, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyi, -R9~GR8, -R9-0C{0}-R8, -R9-N(Re)R7, -R9-C{G}R8, -R9-C(0}0R8, -Rs-C(0)N{R6)R7, -R9-N(R6)C{G)OR8, -R9-N(R6)C(0)R8, -R9-N(R6)S{0)iR8 (where t is 1 or 2), -R9~S(0)t0R8 (where t is 1 or 2), -R9~S(0)pR3 (where p is 0, 1 or 2), and -R9-S(0)iN(R6)R,/ (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haioalkyi, bydroxyaikvl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaikyl, optionally substituted cycioalkylaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclvlalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyi, -R^-GR8, -R10-CN, -R10-NO2, -R10-N(Rs)2, -R;0-C(Q)OR8 and -R10-C(O)N(R8)2, or any R® and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikynyi, optionally substituted cycioaikyl, optionally substituted cycioalkylaikyl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each R10 is an optionally substituted straight or branched alkyiene chain,
63. 64. The compound of Claim 59 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R103-!M(R6a}R?a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted N~heteroaryl or an optionally substituted /V-heterocyclyl, and R10a is an optionally substituted straight or branched aikylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"~OR8s, -R98-C(0)R89i -R®9-C(0)0R8s, -R9s-N(R69)R7s and -R"-C{0)N{RSs)R7s, where each R60, R’9 and R®3 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R®9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; RJ is selected from the group consisting of a bicyclic aryl and a hlcydic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -'R9-OR8, -R9-0C(0)-Ra, ~R9-N(R6}R\ -R9-C(0)Rs, -R9-C(0)CR8, -R9-C(0)N(R8)R7, -R9~N(R6}C(0)QR8, -R9-N(R6)C(G)R8, -R9"N(R6}S(0}tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2}, -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyl, optionaiiy optionally substituted heterocyclyl, optionally substituted beterocyclylslkyi, optionaiiy substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-ORS, -R10-CN, ~R10-NG2, -R10~N(R8}2> -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-beterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionaiiy substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalkyi, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryi, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each R10 Is an optionally substituted straight or branched alkyiene chain.
64. 85, The compound of Claim 64 wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2ais -R10a-N{R6a)R7a where Rea and R?a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted N-heterocyclyl, and Ri0a is an optionally substituted straight or branched alkyiene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R98-C(G)R89, -R"-G(G)QR89, -R9s-N(R6s)R70 and -R"-C(0)N(R69)R7as where each Rb9, R70 and R8g is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R®9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R3 is a bicyolic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -Rs-OC(G)-R3, -R9-N(R6)R7, -R9-C(0)R8, -R®-C(0)0R8, -R9-C(0)N(R6}R7, -R9-N(R®)C(0)0R8, -R9-N(R6)C(G)R8, -R9-N(R6)S(0)sR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0)tN(Re)R'' (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyl, -R10-ORB, -R10-CN, -R'°-N02, ~R10~N(Rs)2, ~R10-C(O)ORs and -R1Q-C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted /V-heterocyclyl; each Rs is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted arafkynyl, optionally substituted cycioaikyi, optionally substituted cycloaikylalkyi, optionally substituted heterocyclyl, optionally substituted heterocyciyialkyl, optionally substituted heteroaryl, and optionally substituted heteroa ry la I kyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.

    66, The compound of Claim 64 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2ais -R10a-N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl, and R10a is an optionally substituted straight or branched aikylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR89, -R"-C{0)R89, -R99~C(G)GR8s, -R"-N(RSg}R79 and -R9s-C(0)N(R6s)R79, where each R®9, R79 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9® is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R3 is a bicyclic heteroaryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, ~R9-QR8, -R9-0C(0)-Rb, -R9-N(R6)R7, -R9-C{0)R8, -R®-C(Q)QR8, -R9-C(G)N(R6)R7, -R9-N(R6)C(0)0Rs, -R9-N(R6)C(Q)R8, -R®-N(R6)S(G)tR8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R0-S(O)PR8 (where p is 0, 1 or 2), and -R9-S(G)tN(Re)R7 (where t is 1 or 2); each R6 and Rr is independent selected from the group consisting of hydrogen, aikyi, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaikyi, optionally substituted cycloaikylalkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyciyialkyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyi, -R10~OR8, -R10-CN, -R10~NO2l -R10-N(R8)2, -R10~C(O)ORs and -R10-C{O)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroary! or an optionally substituted A/-beterocycly!; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted an/l, optionally substituted aralkyl, optionally substituted araikynyi, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionaily substituted heterocyclylalkyl, optionally substituted heieroaryi, and optionally substituted heteroarylalkyi; each R8 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R1u is an optionally substituted straight or branched alkylene chain.

    67. The compound of Claim 59 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R1Qa-N(R0a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroary! or an optionally substituted W-heterocyclyi, and R103 is an optionaily substituted straight or branched alkylene chain; R29 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R8s-ORB9, «R"-C(0)R89, -R99-G(0)0R8s, ~R9s-N(R68)R79 and ~R"~C(G)N(R69)R70, where each R69, R79 and R89 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, ary! and aralkyl, and each RSg is independently selected from the group consisting of a direct bond and an optionaily substituted straight or branched alkylene chain; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryi are each optionaily substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionaily substituted heterocyclyi, optionaily substituted heterocyclylalkenyl, -R9-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9~C(0)R8, -R9-C{0)0R8, -R9-C(G)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0}Rs, -R8'N{R6)S(0)(R8 (where t is 1 or 2), ~R9-S(Q);GR8 (where t is 1 or 2), -R9-S(G)PR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6)R7 (where t is 1 or 2); each Ke and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroaryialkyl, -R10-GR8, -R10-CN, -Ri0-NO2, -R10-N(R8)2, ~R10~C(G)OR8 and -R10-G(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryi or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, and optionally substituted heteroaryialkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

    68. The compound of Claim 67 wherein: R1, R'5 and R6 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-Nj(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted N-heterocyclyi, and R1ua is an optionally substituted straight or branched alkylene chain; R2s is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R"-OR8s, -R"-C(0)R89, -R90-C{G)ORBs, -R"-N(R5s)R79 and -R9s-C(Q)N(Res)R79, where each R6s, R73 and R8s is independently selected from the group consisting of hydrogen, aikyl, haloalkyl, aryl and aralkyl, and each R®s is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a tricyclic aryl optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyciylaikenyl, -R3-ORs, -R9-0C(0)-R8, ~R9-N(R6)R7, -R9-C(G)R8, ~R9-C(G)GR8, -R9-G(Q)M(R6}R7, ~Rs~N(R6)C(G)QR8, -Rs~N(R6)C(G)R8, -R9-N(R6)S{G),R8 (where t is 1 or 2), -R9-S(G)tOR8 (where t is 1 or 2), -R9-S(G)PR8 (where p is 0, 1 or 2), and -R9-S{0)tN(R8)R7 (where t is 1 or 2); each R° and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl. -R10-GR8, -R10-CN, -R10-NO2, -R10-N(R8)2! -R10-G(O)OR8 and -R10-C(O)N(R8)2> or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

    69. The compound of Claim 67 wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2a is -R10a-N{R8a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted W-heferoaryi or an optionally substituted W-heterocyciyl, and R10a is an optionally substituted straight or branched alkylene chain; R23 is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, -R9s-QR8g, -R"-C(0)R89, -RSg-C(0)0R89, -R98~N(R8g)R7s and -R98-C(G)N(R68)R7g, where each Rbs, R73 and R®9 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R" is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is a tricyclic heteroaryi optionally substituted by one or more substituents selected from the group consisting of oxo, haio, haioaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyciyl, optionally substituted heterocyciylaikenyi, -R9-OR8, -R9-0C(0)-R8, -R9~N(R6)R7, -R9-C(0)Rs, -R9-C{G)OR8, -R9~C(0}N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)Rs, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9-S(0)PR8 {where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloaikyl, optionally substituted cycioalkylalkyi, optionally optionally substituted heterocyclyi, optionally substituted heterocyciyialkyl, optionaiiy substituted heteroaryi, optionally substituted heteroarylaikyi, -R10-OR8, -R10-CN, -Ri0-NG2, -R10-N(R8)2i ~R10~C(Q)ORS and ~R10-C(G)N(R8)2, or any R8 and R7, together with the common nitrogen to which they are both attached, form an optionaiiy substituted W-heteroaryi or an optionally substituted AZ-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloaikyl, optionally substituted cycioalkylalkyi, optionaiiy substituted heterocyclyi, optionally substituted heterocyclylaikyl, optionally substituted heteroaryi, and optionally substituted heteroarylaikyi; each R9 is independently selected from the group consisting of a direct bond and an optionaiiy substituted straight or branched aikyiene chain; and each R10 is an optionally substituted straight or branched aikyiene chain.

    70. The compound of Claim 58 having the following formula (!b2):

    wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; R2b is selected from the group consisting of hydrogen, halo, haioaikyl, -R9b-QR6b, -R9b-C(Q)OR8b, -R9b-N(R6b)R7b and ~R9b-C(0)N{R6b}R7b, where each R6b, R7b and Rob is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2cis selected from the group consisting of -C(0)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the beteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haioaikyl, alkyl, eycloalkyi, cycloalkyiaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyciylalkenyi, -R9~OR8, -R9-Q-R10~QRs, -R9-Q-R10-Q-R1q-QR8, -r9-o-r10-gn, ~R9~O~R10~C(O)OR8, ~R9-O~R10~C(O)N(R6)R7, -R9-O~R10-S(O)pR8 (where p is 0, 1 or 2), -R9~Q-R50~N(R6)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-GG(0)-R8, ~R9-iM(R6)R7, -R9-C(G)R8, -R9~C(Q)QR8, ~R9-C(G)N(R6)R7, -R9-N(R6)C(G)0R8, -R9-N(R6)C(G)R8, ~R9~N(R8)S(G),R8 (where t is 1 or 2), -R9-8(0)tQR8 (where t is 1 or 2), -R9-S(0)pRs (where p is 0, 1 or 2), and -R9~S(0)tN(R6)R7 (where t is 1 or 2); each R5 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aikynyl, haioaikyl, haioalkenyl, haloaikynyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyi, optionally substituted aralkynyi, optionally substituted cycloalkyl, optionally substituted cycloalkyiaikyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkyialkynyl, optionally substituted heierocyciyi, optionally substituted heterocyclylalkyl, optionally substituted heterocyciylalkenyi, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryialkynyl, -R10-GR8, -R10~CN, -R10-NG2, -Ri0-R(R8)2, -R10-C(O)OR8 and -R1f,-€{0)N(R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted ary!, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioalkyiaikyl, optionally substituted cydoaikylafkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyciylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroaryialkyi, optionally substituted heteroarylalkenyl, optionally substituted heteroaryialkynyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; each Ri0 is an optionally substituted straight or branched aikylene chain; and each R11 is hydrogen, aikyi, cyano, nitro or -OR8.

    71. The compound of Claim 70 wherein; R1, R4 and R° are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9t'-OR8b, -R9b~C(0)0R8b, -R9b-N(R6b)R7b and -R9b-G(0)N{R6b)R7b, where each R6b, R7b and Reb is independently selected from the group consisting of hydrogen, aikyi, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2cis selected from the group consisting of -C(G)R8, hydrogen, alkyl, an optionally substituted non-bridged cycloalkyl and an optionally substituted bridged cycloalkyi; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyciic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, aikyi, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyciyi, optionally substituted heterocydySalkenyl, -R®-OR8, -R3-QC(0)-Ra, ~R9~N(R6)R7, -R9-C{0)R8, -R9-C(0)0R8, -R9~C(G)N(R6)R7, -R9~N(R6)C(0)0R8, -R9~N(R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9-S(0),0R8 {where t is 1 or 2), -R9-S(G)PRs (where p is 0, 1 or 2), and -Rs-S(0}!N(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, bydroxyalkvl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycioaikylalkyl, optionally optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, optionally substituted heteroarylaikyl, -R1c'-OR8, -R10~CN, -R10-NG2, ~R10~N(R8}2, ~R10-C(O)QR8 and -R10-C(G)N(R8)2, or any Re and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroary! or an optionally substituted A/-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyi, optionally substituted cycioaikylalkyl, optionally substituted heterocyciyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, and optionally substituted heteroarylaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each Ria is an optionally substituted straight or branched aikylene chain.

    72, The compound of Claim 71 wherein; R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-ORSb, -R9b-C(0)0R8b, -R9b-N(R*)R7b and -R9b-C(0)N(R6b)R7b, where each Reb, R7b and RSb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2c is selected from the group consisting of -C(0)R8, hydrogen and alkyl; R2K is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyclic ary! and a monocyclic heteroaryi, where the monocyclic aryi and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, baloaikyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyolyi, optionally substituted heterocyciylalkenyl, -R9-ORs, -R9-GC(Q)-R8, -R9-N(K®)R7, -R9-C(G)R8, -R9-C(0)GR®, -R9-C(0)N(R6)R7, ~R9-N(R6)C{0)QR8, -R9-N(R6)C(G)R8, -R9-N(R6)S(0),R8 (where t is 1 or 2), -Rs~S(Q),OR8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and ~R8-S(G)iN(Rs)R7 (where t is 1 or 2); each Rs and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaSkyl, optionally substituted cycloaikylalkyl, optionally optionally substituted heterocyolyi, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(Re)2, -R10-C(O)QR8 and -R10-C(O}N(R8)2, or any R6 and R'. together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted N-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycioaikyl, optionally substituted cycloaikylalkyl, optionally substituted heterocyolyi, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, and optionally substituted heteroarylaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; and each R!Q is an optionally substituted straight or branched alkyiene chain.

    73. The compound of Claim 71 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-QR8b, -R9b-C(G)QR8b, -R9b-N(R6b)R7b and -R9b-C{0}W(R6b)R7b, where each R6b, R7b and R8b is independentiy selected from the group consisting of hydrogen, aikyl, haloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkyiene chain; R2c is an optionally substituted non-bridged cycioaikyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a monocyciic ary! and a monocyclic heteroaryl, where the monocyciic aryl and the monocyclic heteroaryi are each optionaliy substituted by one or more substituents selected from the group consisting of haio, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyi, -R®-OR8, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N{R6)C(0)0Rs, -R9-N(R5)C{0}R8, -R9-N(R6)S(G)tR8 (v/here t is 1 or 2), -R9-S(0),0R8 {where t is 1 or 2), -R9-S{G)PR8 (where p is 0, 1 or 2), and -R9~S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cvcloalkyl, optionally substituted cycioaikylalkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroaryialkyl, -R10~OR8, -R10-CN, -R1g-N02, -R10-N(R8)2, ~R10-C(G)GR8 and -R10-C(O)N(R8)2! or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionaliy substituted /V-heteroeydyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycioaikyl, optionally substituted cycioaikylalkyi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, and optionally substituted heteroaryialkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R1t> is an optionally substituted straight or branched alkylene chain.

    74, The compound of Claim 71 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZb is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-OR8b, -R9b-C(G)ORab, ~R9b~N(R6b)R7b and -RSb~C(0)N(R6b)R7b, where each Rsb, R7b and RBb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each RSb is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; RZc;s an optionally substituted bridged cycloalkyl; Rzk is selected from the group consisting of hydrogen and alkyl; R3 Is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryi, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloaikyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyi, optionally substituted heterocyclylalkenyl, -R9-QR8, ~R9-QC(0)-R8t -R9-N(R6)R7, -R9-C(0)R8, -R9~C(G)OR8, -Rs~C(0)N(R6)R?, -R9-N(R6)C(G)OR8, -R9~N(R6)C{0)R8, -R9~N(R6)S(G)tRs (where t is 1 or 2), ~Rs-S(G}.OR8 (where t is 1 or 2), ~R9-S(Q)PR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6)R7 (where I is 1 or 2); each R8 and R' is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyi, optionally optionally substituted heterocyclyi, optionally substituted heterocyciyiaikyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R10-NO2, -R10-N(R8)a, -R10-G(O)OR8 and -R10-C(O)N(Rs)2, or any R6 and R', together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted /V-heterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikynyl, optionally substituted cycloaikyi, optionally substituted cycloalkylalkyi, optionally substituted heterocyclyi, optionally substituted heterocyciyiaikyi, optionally substituted heteroaryi, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; and each R10 is an optionally substituted straight or branched aikyiene chain.

    75. The compound of Claim 70 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; RZb is selected from the group consisting of hydrogen, halo, haloaikyl, -R9B-GR8b, -R^-CfOpR88, -R9b-N(R6b}R7b and -R9b~C(0)N{R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alky!, haloalkyl, ary] and aralkyl, and each RSb is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis selected from the group consisting of -C(0)R8, hydrogen, aikyi, an optionally substituted non-bridged cycloaikyl and an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroeyciyl, optionally substituted heterocyclylalkenyl, -R9-OR6, -R9~QC{G)~R8, -R9-N(R6)R7, -R9~C{Q)R8, -R9~C(G)QR8, -R9-C(G)N(R6)R7, -R9~N(R6)C(0)0R8, -R9~N(Re)C{G)R8, -R®-N(R®)S(0)tR8 (where t is 1 or 2), -R9-S(0)iQR8 (where t is 1 or 2), -R9-S(Q)PR® (where p is 0, 1 or 2), and -R9~S(0),N(R6)R7 (where i is 1 or 2); each R8 and R7 is independently selected from the group consisting of hydrogen, alky], haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaikvl, optionally substituted cycloalkylalkyl, optionally optionally substituted heteroeyciyl, optionally substituted heterocyclyialkyi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R1C'-0R8, -R10-CN, -R1U~N02, -R10-N(R8)2i ~R10-C{O)OR8 and -R10~C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted (V-heteroaryl or an optionally substituted W-heterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloaikyl, optionally substituted cycloalkylalkyl, optionally substituted heteroeyciyl, optionally substituted heterocyclyialkyi, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

    76. The compound of Claim 75 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haioaikyi, -R9D-OR8b, -R9b“C(Q)QR8b, -R9b-M(R6b)R7b and ~R3b-C(0)fM{R6b)R7b, where each R®\ R7b and Rsb is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2cls selected from the group consisting of ~C{G)R8, hydrogen and alkyl; R2k is selected from the group consisting of hydrogen and aikyl; R2 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryi, where the bicyclic aryl and the bicyciic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyi, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyciyi, optionally substituted heterocyclylalkenyl, -R9-QR8, -R9-OC{G)-R8, ~R9-N(R6)R?, -R9~C{Q)R8, -R9-C(G)OR8, -R8-C(0}IM(R6)R7, -R9-N(R®)C(0)GR8, ~R9-N(R6)C(0)R8, -R9-N(R®)S(0)tRs (where t is 1 or 2), -R9-S(0)t0R8 (where 1 is 1 or 2), -R9-S(G)PRs (where p is 0, 1 or 2), and -R9-S(0)tN(R®)R7 (where t is 1 or 2); each K6 and R7 is Independently selected from the group consisting of hydrogen, aikyl, haioaikyi, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycioaikyialkyi, optionally optionally substituted heterocyciyi, optionally substituted heterocyclyialkyl, optionally substituted heteroaryi, optionally substituted heteroarylaikyl, -R10-QR8, -R10-Chi, ~R10~NO2, -R10-N(R8)2, ~R10~C(O)OR8 and -R10-G(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted ^/-heterocyciyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioaikyialkyi, optionally substituted heterocyciyi, optionally substituted beterooyclylalkyl, optionally substituted heteroaryi, and optionally substituted heteroarylaikyl; each R9 is independently selected from the group consisting of a direct bond and an optionaiiy substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

    77, The compound of Claim 76, which is 1-{6-chloroqu!nazoiin-4"yl)“/V5-(4-(4~ methylpiperazin-1 -yi)phenyl)-1 H-1,2,4-triazole-3,5-diamine.

    78. The compound of Claim 75 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b-QR8b, -R9b-C{G)ORab, -Rsb-N(R5b)R7b and ~R9b~C(0)N(Reb)R7b, where each R6b, R7b and RSb is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R90 Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis an optionally substituted non-bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic ary! and a bicycilc heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenvl, -R9-OR8, -R9-0C(0)-R8, -R9-N(Re)R7, -R9-C(Q)R8, -R9-C(0)GR8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9~N(R6)C(Q)Rs, -R9~N(R8)S(0)tR6 (where t is 1 or 2), -R9~S{Q),OR8 (where t is 1 or 2), -R9~S(G)PR8 (where p is 0, 1 or 2), and -R9~S{Q)tN(R6)R7 (where t is 1 or 2); each R6 and R7 Is independently selected from the group consisting of hydrogen, aikyi, haloalkyl, bydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloaikyl, optionally substituted cycloaikyiaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclyiaikyi, optionally substituted heteroaryi, optionally substituted heteroarylalkyl, -R10-GR8, -R'°-CN, ~R10~NO2, -R10~N(R8}2, -R10-C(O)OR8 and ~R10~C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryi or an optionally substituted iV-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyi, optionally substituted cycioaikylalkyl, optionally substituted heierocyciyi, optionally substituted beterocyclyialkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain,

    79. The compound of Claim 78, which is /V*-(4-(4-cyclohexylplperazin-1- yl)phenyl)-1-{6,7-dinethoxyquinazoiin-4-yl )-1 H-1,2,4-ihazole-3,5-diamine.

    80. The compound of Claim 75 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b~OR8b, -R9b-C(Q)OR8b, -R9b-N(R6b)R7b and -R9b-C(0)N(R6b)R?b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each RSb is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2ols an optionally substituted bridged cycloalkyi; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heierocyciyi, optionally substituted heterocyclyialkenyi, -R9~QR8, -R9-0C{0)-R8, -R9-N(R6)R7, -R9~C(0)Rs, -R9~C(0)GR8, -Rs-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, -R9-N(K6)C(Q)R8, ~R9-N(K6)S(0)tR8 (where t is 1 or 2), -R9-S(0)j0R8 (where t is 1 or 2), -R8-S(0)pR8 (where p is 0, 1 or 2), and -Rs-S(0),N(Rs)R7 (where t is 1 or 2): each R6 and R7 is Independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyi, optionally substituted cycioaikylalkyl, optionally optionally substituted beterocydyl, optionally substituted beterocyclylalkyi, optionally substituted heteroaryl, optionally substituted heteroaryialkyl, -R^-OR8, -R10-CN, -R10-NG2, -R10-N{R8)2, -R10-C(O}ORs and -R10-C(O)N{R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocydyiaikyl, optionally substituted heteroaryl, and optionally substituted heteroaryialkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

    81. The compound of Claim 80 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyi, -R9b-OR8b, -R9b-CfO)OR8B, -RBb-M(RSb)R7b and -R9s-C(Q)N(R6b)R7b, where each R6b, R7b and RSb is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2cis optionally substituted bicyclo[2.2.1]heptanyl; R2k is selected from the group consisting of hydrogen and alkyl; R“ is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryl and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyi, aikvl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclyiaikenyl, -RS-QRS, -R9~0C(0)~R8, -R9-N(R6}R7, -R9-€(0)R8, -R9-C{0)0Rs, -R9-C{0}N(R6)R7, -R9-N(Rs}C{0)GR8, -R9-N(R6)C(0)R8, -R9“N(R6)S{0)tR8 (where t is 1 or 2), -R9”S(G)tOR8 (where t is 1 or 2), -R9-S(Q)PR8 (where p is 0, 1 or 2), and -R9"S(0)tN(R8)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycioaikylalkyi, optionally optionally substituted heierocyclvl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-GR8, -R10-CN, -R10~NO2, ~R1q-N{R8)2, ~R10~C(G)OR8 and -R1D-C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocyciyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikynyl, optionally substituted cycloalkyi, optionally substituted cycioaikylalkyi, optionally substituted heterocvciyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each Rs is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.

    82. The compound of Claim 81 selected from the group consisting of; 1 -(6-(1,1~dimethylethyi)thieno[3!2~d]pyrimidin~4-yn~/V5-{4-(4-(bicyclo[2.2.1]heptan-2-yl)-piperazin-1 ~yl)pheny!}-1 H~ 1,2,4-triazole-3,5-diamine; 1~(benzo[d]thiazol-2-yi)-W5-(4-{4-(blcycio[2.2.1]heptan-2-yi)piperazin-1-yi)phenyl)-1H- 1,2,4-triazole-3,5-diamine; and A/5-{4-(4-(bicycio[2.2.1]beptan-2-y!)piperazin-1-yl)phenyl )-1-(6,7-dimethoxyquinazoiin-4-yl)-1 H-1,2,4-triazole-3,5-diamine.

    83. The compound of Claim 70 wherein: R\. R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkyl, -R9b~OR8b, -R9b~C(Q)QR0b, -R9b~N(R6b)R7b and -R9b-C(0)N(R6b}R7b, where each Reb, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9b Is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is selected from the group consisting of -C(0}Rs, hydrogen, alkyl, an optionally substituted non-bridged cycioalkyl and an optionally substituted bridged cycloalkyi; R2k is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heieroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9~QR8, -R9-0C(0)~R8, -R9-N(R6)R7, -R9-C(G)R8, -R9~C£0)QR8, -R9~C(Q)N(Rs)R7, -R9-N(R6)C(0)GR8, -R9-N(Re)C(G)R8, ~R9-N(R6)S(G)tR8 (where t is 1 or 2), -R9-S(Q)tOR8 (where t is 1 or 2), -R®-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(G)tN(R6}R7 (where t is 1 or 2); each Rfe and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, -R10-CN, -R30-NQ2i -R1c-N(R8)2, ~R10~C(O)OR8 and -R10-C(O)N(Rs)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted W-heterocyciyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalky!, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 Is an optionally substituted straight or branched alkylene chain,

    84. The compound of Claim 83 wherein: R1, R"5 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2d Is selected from the group consisting of hydrogen, halo, haloalkyi, -R9b-OR8B, -R9b-G(Q)OR8b, -R9b-N(R6b)R7b and ~R9b-C(0)N(R6b)R7b, where each K6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, baloalkyl, aryl and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R&amp; is selected from the group consisting of -C(G)R8, hydrogen and alkyl; R2* is selected from the group consisting of hydrogen and alkyi; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryi, where the tricyciic aryi and the tricyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterccyclylalkenyl, -R9-QR8, -R9-GC{O)~R0, -Rs-N(R6)R7, -R9~C(0)R8, -R9~C(G)OR8, -R9-C(0)N{R6)R7, -R9-N(R6}C(0)GR8, -R9-N{R6)C(0)R8, «R9-N(R6)S(0)sR8 (where t is 1 or 2), -R9-S{G)iORs (where t is 1 or 2), -R9-S(Q)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocvclyialky!, optionally substituted heteroaryi, optionally substituted heteroarylalkyi, -R10-OR8, -R10-CN, -R10-NO2, ~R1g-N(R8)2, -R10-C(O}QR8 and -R1Q-C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryl or an optionally substituted W-heterocyciyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyciylaikyi, optionally substituted heteroaryi, and optionally substituted heteroarylalkyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R'° is an optionally substituted straight or branched aikylene chain,

    85. The compound of Claim 83 wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloaikyi, -R9b-OR8°, -R9b-C(0)QR8b, -R9b~N(R6b)R7b and -R9b-C(0)N(R6b)R7b, where each R6b, R7b and R8b is independently selected from the group consisting of hydrogen, alkyl, haloaikyi, ary! and aralkyl, and each R9b is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R2c is an optionally substituted non-bridged cycloalkyl; Ra is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryi, where the tricyclic aryi and the tricyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloaikyi, alkyl, optionally substituted aryi, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyi, -R9-OR8, -R9-GC(0)~R8, -R9-N{R6)R7, -R9-C(Q)Rs, -R9-C(G)GR8, -Re-C(0)N(Re)R7, -R9-N(R®)C(Q)OR8, ~R9-N(R6)C(0)R8, -R9-N(R6)S(G)tR8 (where t is 1 or 2), -R9-S(0)tGR8 (where t is 1 or 2), -R9-S(G)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, alkyl, haloaikyi, hydroxyaikyi, optionaliy substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionaliy substituted heteroaryi, optionally substituted heteroarylalkyl, -R10~GR8, -R10-GN, -R10-NO2, -R10-N{Rs)2, -R10-C(O)QR8 and -R1Q-C(0)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted A/-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloaikyi, optionally substituted aryi, optionally substituted aralkyl, optionally substituted araikynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heteroaryi, and optionally substituted heteroarylalkyl; each Rs is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkyiene chain.
65. 86, The compound of Claim 85 which is 1-(phenanthridin-6-yl)-/V®-(3-fluoro-4- (4-cycIopentylpiperazin-1-yl)pheny! )-1 W-1,2,4-triazole-3,5-diamine.
66. 87. The compound of Claim 83 wherein: R1, R4 and Rb are each independently selected from the group consisting of hydrogen and alkyl; R2b is selected from the group consisting of hydrogen, halo, haloalkvi, ~R9b~OR8b, -R9b-C(0)0R8b, ~R9b~N{Reb)R7b and -R9b-C(0)N(R6b)R7b, where each R0b, R7b and RSB is independently selected from the group consisting of hydrogen, aikyl, haioaikyl, aryl and aralkyl, and each R9b is Independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; R2cis an optionally substituted bridged cycloalkyl; R2k is selected from the group consisting of hydrogen and aikyl; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryi, where the tricyclic ary! and the tricyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyl, alkyl, optionally substituted aryl, optionaliy substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyi, -R9-OR8, -R9-0C(0)-Rs, -R9-N(R6)R\ -R9"C(G)R8, -R5-C{0)0R8, -R9-C(G)N(Re)R?. -R9-N{R6)G{0)0R8, -Re-N(Re)C(0)R8, -R^NiR^SiOfcR8 {where t is 1 or 2), -R9-S(0)s0R8 (where t is 1 or 2), -R9-S(0)pR8 {where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each Rs and R7 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, hydroxyaikyl, optionally substituted aryi, optionally substituted aralkyl, optionally substituted cvcloalkyi, optionally substituted cycloaikyialkyi, optionally optionally substituted heterocyclyl, optionally substituted heterocyclyiaikyS, optionally substituted heteroaryi, optionally substituted heteroarylaikyl, -R10-OR8, -R10-C!M, -R1Q~N02, -R10-N(R8)2) ~R1d~G(0)GR8 and -R10-C(Q)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroaryi or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioaikylalkyl, optionally substituted heterocyclyl, optionally substituted beterocyclylalkyl, optionally substituted heteroaryi, and optionally substituted heteroarylalkyi; each R® is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkyiene chain.
67. 88. The compound of Claim 58 having the following formula (ib3):

    wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C{0)R8 and -C(G)N(R6)R7; RZe is selected from the group consisting of halo, -OR8, -C(Q)RS, -C(G)OR8, -R10e-N(R6)R7, -R10e-C(O)N(R6)R7, optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R1Cte is an optionally substituted straight or branched alkylene chain: R2“ and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloaikyl, alkyl, cycloalkyl, cycioaikylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyi, optionally substituted heteroarylaikenyi, optionally substituted heterocyclyl, optionally substituted heterocyclyialkyi, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-aR10-GRs, -R9-G-R10~O~R10~GR8, -r9~o-r10~cn, -R9-0-R1q-C(Q)OR8, -R9-0-R10-C(0)N(R6)R7, -R9-0-R'q-S(0)pR8 (where p is 0, 1 or 2), -R9-Q-R10-N(R6)R7, -Rs~O~R10-C(NR11)N(R11)H, -R9-0C(0)-R3, -R9-N(R6)R7, -R9-G{G)R8, ~R9-C(0)QR8, -R9~C{0)N(R6)R7, -R9-N(R6)C(G)OR8, -R9-N{R6)C(0)R8, ”R9"N(Rs)S{0)tR8 {where t is 1 or 2), -R9-S{0),0R8 (where t is 1 or 2), ~R9-S(G)PR8 (where p is 0, 1 or 2), and -R9-S{G)tN(R6)R7 (where t is 1 or 2); each R6 and R7 are each independently selected from the group consisting of hydrogen, aikyi, alkenyl, alkynyl, haioalkyi, haloalkenyi, haioaikynyl, hydroxyaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyi, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloaikylalkyl, optionaiiy substituted cycioaikylalkenyl, optionally substituted oycioaikyialkynyl, optionally substituted hetarocyclyi, optionaiiy substituted heterocyclylaikyl, optionally substituted heterocyclyialkenyi, optionaiiy substituted heterocydyialkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroaryialkenyl, optionaiiy substituted heteroarylalkynyi, ~R10~OR8, -R10-CN, -R10-NO2> -R10~N(R8)2, ~R10-C{O)OR8 and -R1c'-C(G}N(RB)2! or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionaiiy substituted W-heteroary! or an optionally substituted /V-heierocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haioalkyi, haloalkenyi, haioaikynyl, optionally substituted ary!, optionaiiy substituted aralkyi, optionally substituted araikenyi, optionally substituted aralkynyl, optionaiiy substituted cycloalkyi, optionaiiy substituted cycioalkyialkyi, optionaiiy substituted cyeloalkyialkenyi, optionally substituted cycloalkyialkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heterocyclyialkenyi, optionaiiy substituted heterocyclylaikynvi, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroaryialkenyl, optionally substituted heteroarylalkynyi; each R0 is independently selected from the group consisting of a direct bond or an optionally substituted straight or branched alkyiene chain; each R10 is an optionaiiy substituted straight or branched alkyiene chain; and each R11 Is hydrogen, alkyl, cyano, nitro or-OR8.
68. 89. The compound of Claim 88 wherein; R1, R4 and R6 are each independently selected from the group consisting of hydrogen and alkyl; R2e is selected from the group consisting of haio, -OR8, -C(0)Rs, -C(G)OR8, -R10e-N(R6)R7, -R108-C{0)N(R6)R7> optionally substituted heterocyciyi and optionally substituted heteroaryl, where each R10s is an optionally substituted straight or branched aikylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alky! and -OR8; R3 Is selected from the group consisting of a monocyclic aryl and a monocyclic heteroaryl, where the monocyclic aryl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of haio, haloalkyi, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyciyi, optionally substituted heterocyclyialkenyl, -R9-GR8, ~R9-GC(0}-R8, -R8~N(R6)R7, -R9-C(0)R8, -R9~C(G)OR8, -R9-C(0)N{R6)R7, -R9-N(R®)C(0}0R8, -R9-N(R6)C(G)R8, -R9-N(Re')S(G)tR8 (where t is 1 or 2), -R9-S(0)t0R8 (where t is 1 or 2), -R9~S(0)pR9 (where p is 0. 1 or 2), and -R9-S(0)sN(R6)R7 (where t is 1 or 2); each Rs and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyiaikyi, optionally optionally substituted heterocyciyi, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R10~OR8, -R10-CN, ~R10~NO2, -R10-N(R8)2i ~R10-C(O)OR6 and -R10-C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyciyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkyiaikyi, optionally substituted heterocyciyi, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 is an optionally substituted straight or branched aikylene chain.
69. 90. The compound of Claim 88 wherein; R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2e is selected from the group consisting of halo, -OR®, -C{0)R8, -C(0)0R8, ~R10e~N{R6)R7, -R10e-C(O)N(Re)R7 optionally substituted heterocyclyl and optionally substituted heteroaryl, where each R10e is an optionally substituted straight or branched aikylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of a bicyclic aryl and a bicyclic heteroaryl, where the bicyclic aryi and the bicyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -R9-OR8, -R9-QC(Q)-R8, -R9-N(R6)R7, -R9-C(0)R3, -R9-C(Q)GR8, -R9-C(0)N(R6)R?, -R9-N{R6)C{0}0Rs, -Rs~N(R6}C{Q}R3, -R9-N{R6)S(Q)iR8 (where t is 1 or 2), -R9-S(0)tGR8 (where t is 1 or 2), -R9-S(0)pR3 (where p is 0, 1 or 2), and -R9-S(0)jN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalky!, optionally substituted cycloalkylalkyi, optionally optionally substituted hetorocyciyi, optionally substituted heterocyciylalkyl, optionally substituted heteroaryl, optionally substituted heteroaryialkvi, -R10-GRS, -R10-CN, -R10-NO2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-C(O)N(R8)2, or any R6 and R', together with the common nitrogen to which they are both attached, form an optionally substituted i¥-beteroary! or an optionally substituted AZ-beterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haioalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionally substituted cycloalky!, optionally substituted cycloalkylalkyi, optionally substituted heterocyclyl, optionally substituted heterocyciylalkyl, optionally substituted heteroaryi, and optionally substituted heteroarylalkyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each R10 Is an optionally substituted straight or branched aikylene chain.
70. 91. The compound of Claim 90 selected from the group consisting of: (V5..(4.({1..methylpyrrolidin-2-yi)methoxy)phenyi)-1-{quinoxalin-2-yI)-1H-1J2,4-triazoie-3,5- diamine; 1-(6,7-dsmethoxyquinazQ!in~4-y1)~W5-(4~(1~methy!piperidin~3-ytoxy)phenyi)-1W-1,2,4~ triazole-3,5-diamine: and 1-(isoqu!noiin-1-yi)-N5"(4-morphoiinophenyl)”1H-1)2,4"triazole-3)o-diamine.
71. 92, The compound of Claim 88 wherein: R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2® is selected from the group consisting of halo, -OR8, -C(Q)R8, -C(0)0RB, -R10e-N(R6)R7, -R102-C{G)N(Re)R?, optionally substituted heterocyciyi and optionally substituted heteroaryi, where each R1Cs is an optionally substituted straight or branched alkylene chain; R2d and R2f are each independently selected from the group consisting of hydrogen, halo, alkyl and -OR8; R3 is selected from the group consisting of a tricyclic aryl or a tricyclic heteroaryi, where the tricyclic aryl and the tricyclic heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyciyi, optionally substituted heterocyclylalkenyl, -R9-QR8, -R9-GC(Q)-R8, -R9-N(R6}R7, -R9-C(G)R8, “R9-C(0}0R8, -R9-C(0)N{R6}R7, ~R9-N(R6)C(Q)GR8, ~R8-N(R6)C(G)R8, -R9-N(R6}S{Q)tR8 (where t is 1 or 2), -R9-S(0)sQR8 (where t is 1 or 2), -R9-S(G)PR3 (where p is 0, 1 or 2), and -R9-S(0),N(R6)R? (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, aikyi, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally optionally substituted heterocyciyi, optionally substituted heterocyciylalkyl, optionally substituted heteroaryi, optionally substituted heteroarylaikyl, -R10~QR8, -R10-GN, -R10-NO2, ~R'°-N(R8)2, -R10~C(Q)QR8 and -R10-C(Q)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-beteroaryl or an optionally substituted W-heterocyclyi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioaikyialkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted beteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
72. 93. The compound of Claim 58 having the following formula (Ib4):

    wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryi, aralkyl, -C(0)R8 and -C{0)N(R6)R7; R2h is selected from the group consisting of hydrogen, -N(RSh)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryi, where RBh is hydrogen or alkyl and R7h is an optionally substituted bridged cycioaikyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR3 and -R9-N(R6)R7; R2i, R2i and R2j are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of aryl and heteroaryi, where the ary! and the heteroaryi are each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloaikyi, alkyl, cycioaikyl, cycioaikyialkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyl, optionally substituted heteroaryiaikenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heierooydyialkenyi, -Rs-OR8, -R9-O-R10-OR8, -R9-O-R1q-O-R10-GR8, "R9-0-R10-GN, -R9-Q-R10~C(O)GR6, -R9-O~R10-G(O)N(R6)R?, -R9~O-R10-S(G)pR8 (where p is 0, 1 or 2), -R9-O-R10-N(R6}R7, -R9-O-R10-C(NR11)N(R11)H, -R9-0C(0}-R8, ~R9-N(R6)R7, -R8-C{0)Rs, -R9-C(0}0R8, -R9-C(0)N(R6)R7, -R9-M(R6)C(0)QR8, -R8-N{R6)C(0)R8, -R9-N(R6)S(0)tR8 (where t is 1 or 2), -R9~S(0),0R8 (where t is 1 or 2), ~R9-S(G)pR8 (where p is 0, 1 or 2), and -R9-S(0),N(R°)R7 (where I is 1 or 2); each R6 and R7 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyi, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyi, optionally substituted aralkynyl, optionally substituted cycloalkyi, optionally substituted cycloaIkylaIkyI, optionally substituted cycloaikylalkenyl, optionally substituted cycloaikylaikynyl, optionally substituted heterocyclyl, optionally substituted heterocyciyialkyl, optionally substituted heterocycSylaikenyl, optionally substituted heterocyclylalkyny!, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R10-QR8, -R10-CN, -R10-NG2, -R10-N(R8)2, -R10-C(O)OR8 and -R10-G{Q)N(R8}2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyi, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyi, optionally substituted aralkenyi, optionally substituted aralkynyl, optionally substituted cycloalkyi, optionally substituted cycioalkyialkyl, optionally substituted cycloalkylaikeny!, optionally substituted cycloaikylaikynyl, optionally substituted heterocyclyl, optionally substituted heterocyciyialkyl, optionally substituted heterocyclylalkenyi, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryi, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond or an optionally substituted straight or branched alkylene chain; each R10 is an optionally substituted straight or branched alkylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or -OR8.
73. 94. The compound of Claim 93, wherein; R\ R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2h is selected from the group consisting of hydrogen, ~N{R6h)R?h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where R6h is hydrogen or alkyl and R,h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(Rs}R7; R2f, R2' and R2i are each independently selected from the group consisting of hydrogen, haio and -OR8; R3 is selected from the group consisting of a monocyclic ary! and a monocyclic heteroaryl, where the monocyclic arvl and the monocyclic heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heterocyclyialkenyi, -R9-OR8, -R9-0C{0)-R8, -RS-N(R6)R7, -R9-C{G)R8, -R9-C(Q)GR8, -R9-C(G)N{R6)R7, -R9~N(R6)C{0)0R8, -R9~N(R6)C(G)R6, -R9-N(R6}S(OXR8 (where t is 1 or 2), -R9-S(0)tGR8 (where t is 1 or 2), -R9-S(0)PR8 (where p is 0, 1 or 2), and -R8-S(0)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyi, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyi, optionaliy optionally substituted heterocyclyl, optionally substituted heterocyciyialkyi, optionaliy substituted heteroaryl, optionally substituted heteroarylalkyl, -R10-OR8, ~R10~CN, -R10-NO2, ~R10~N(R8}2, -R10-C(O)OR8 and -R1D-C(0)N{R8)2, or any Re and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryi or an optionally substituted A/-heterocyc!yi; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylaikyi, optionally substituted heterocyclyl, optionaliy substituted heterocyciyialkyi, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikyiene chain; and each R10 is an optionally substituted straight or branched aikyiene chain.
74. 95. The compound of Claim 93, wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2*1 is selected from the group consisting of hydrogen, -N(R8h)R7h, optionally substituted heterocyclyl and optionally substituted heteroaryl, where R6h is hydrogen or alkyl and R7h is an optionally substituted bridged cycloalkyl; R2d is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2f, R2i and R21 are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a bicyclic ary! and a bicyciic heteroaryl, where the bicyciic aryl and the bicyclic heteroary! are each optionally substituted by one or more substituents selected from the group consisting of oxo, halo, haioaikyi, alkyl, optionally substituted aryl, optionally substituted heteroary!, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -Rs-OR8, -R9-OC(G)-R8, -R9~N{R6)R7, -R9-C(0)R8, -R9-C(0)0R8, -Rs-C(0)N{R6)R7, -R9-N(R6)C{G)OR8, -R9-N(R6)C(G)R8, -R9-N{R6)S(G}.Rs (where t is 1 or 2), -R9-S(0}tORs (where t is 1 or 2). -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(0}{N(Rb)R7 (where t is 1 or 2); each R6 and R7 Is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, hydrcxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycioaikyl, optionally substituted cycloalkyiaikyl, optionally optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, -R10-OR8, -R10~CN, -R10-NO2, -R10-N(Re)2, -R,0-C(Q)OR8 and ~R10~C(O)N(R8)2, or any R6 and R?, together with the common nitrogen to which they are both attached, form an optionally substituted Af-heteroary! or an optionally substituted W-heterocyclyl; each R° is independently selected from the group consisting of hydrogen, alkyl, haioaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyl, optionally substituted cycioaikyl, optionally substituted cycloalkyiaikyl, optionally substituted heterocyclyl, optionally substituted heterocyclylaikyl, optionally substituted heteroaryl, and optionally substituted heteroarylaikyl; each Rs is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched aikylene chain; and each Ri0 is an optionally substituted straight or branched aikylene chain.
75. 96. The compound of Claim 93, wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R2i’ is selected from the group consisting of hydrogen, -N{R6h)R7h, optionally substituted heterocyclyl and optionaliy substituted heteroaryi, where Reh is hydrogen or alkyl and Rrh is an optionally substituted bridged cycloalkyl; R20 is independently selected from the group consisting of hydrogen, halo, -OR8 and -R9-N(R6)R7; R2!, R2i and R2’ are each independently selected from the group consisting of hydrogen, halo and -OR8; R3 is selected from the group consisting of a tricyclic aryl and a tricyclic heteroaryl, where the tricyclic aryl and the tricyclic heteroaryi are each optionaliy substituted by one or more substituents selected from the group consisting of oxo, halo, haloaikyi, alkyl, optionally substituted aryl, optionally substituted heteroaryi, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, -RS~GR8, -R9-OC(G)-R8, ~R9-N{R6)R7, -R9~C(G)R8, -Rs~C(0)0R8, -R9-C(O)N{Rs)R7, ~R9-N{R6}C(0)0R8, -R9-N(R6)C(G)R8, ~R9-N(R6)S(0)*R8 (where t is 1 or 2), -R9-S(0)t0RB (where t is 1 or 2), -R9-S(0}pR8 (where p is 0, 1 or 2), and -R9-S(0}tN(R6}R7 (where t is 1 or 2); each Rs and R7 is independently selected from the group consisting of hydrogen, alkyl, haloaikyi, hydroxyaikyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionaliy substituted cycloalkyiaikyl, optionally optionaliy substituted heterocyclyl, optionally substituted heterocyclyiaikyi, optionally substituted heteroaryi, optionally substituted heteroarylaikyi, -R10-OR8, -R10-CN, -R10-NQ2p -R10~N(R8)2> -R10-C(O)OR8 and ~R10-C(O)N(R8)2l or any R6 and R?, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted /V-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, haloaikyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkynyi, optionaliy substituted cycloalkyl, optionally substituted cycloalkyiaikyl, optionally substituted heterocyclyl, optionally substituted heterocyclyiaikyi, optionally substituted heteroaryi, and optionally substituted heteroarylaikyi; each R9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and each R10 is an optionally substituted straight or branched alkylene chain.
76. 97. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of formula (I): r3 N-l-N I \ wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)Rs and -C(Q)N(R6)R7; R2 is aryl optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haioalkyl, alkvf, cycloalkyl, cycloalkylalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylafkyl, optionally substituted heteroaryiaikenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heterocyclylalkenvl, -R9~OR8, -R9"O-R10-OR8, -R9"O-R10-O-R'°-OR8, ~R9-0~R10-CN, -Rs~Q-K10~C(G)QR8, -R9-O-R10-C(Q)N{R6)R7, -R9”O"R10-S{O)pR8 (where p is 0, 1 or 2), -R9-O~R10~N(R6)R7, -R9-0-R1 °-C(NR11 )N(R11 )H, -R9~OC{G)-R8, -R9~N(Re)R7, -R9-C(0)R8, -R9-C(0)0Rs, -Rs-C(0)N(Re)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -R9~N(R6)S(0),R8 (where t is 1 or 2), -R9~S(Q}tQR8 (where t is 1 or 2), -R9~S{G)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2): R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haioalkyl, alkyl, cycloalkyl, cycloalkylalkyi, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaryialkyl, optionally substituted heteroaryiaikenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heterocyciylaikenyl, ~RS~GR8, -R9-0-R'°~0R8, -R^G-R^-Q-R^-OR8, -Rs~0-R'°-CN, -R®-O-R10-C(O)QR8, -R9-O-R10-C(G)N(R6)R7, -R9~G-R10-S(O)PR8 (where p is 0, 1 or 2), ~Rs-O-R10-N(Re)R7, -R9-O-R10-C(NR11)N(R11)H, -R9-OC(Q)-Rs, -R9-N(Re)R?, -R9~C(Q)R8, -R9-C(0)0R8, -R9-C(0)N(R6)R7, -R9-N(R6)C(0)0R8, ~R9-N(R6)C{0)R8, ~R9-N(R6)S(G)tR8 (where t is 1 or 2), -R9"S(0)tORs (where t is 1 or 2), ~R9-S(G)PR8 (where p is 0, 1 or 2), and -R9-S(0)tN(R6)R7 (where t is 1 or 2); each R® and R7 is independently selected from the group consisting of hydrogen, aikyi, alkenyl, alkynyl. haloalkyi, haloalkenyi, haioalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkeny!, optionally substituted aralkynyl, optionally substituted cycloalky!, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclySalkyl, optionally substituted heterocvclylalkenyl, optionally substituted heterocyclyialkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroaryiaikenyi, optionally substituted heteroarylalkynyl, -R10-GR8, -R10-CN, -R10~NG2, -R10-N(R3)2, -R10-C(O)ORa and -R10-C(O)N(Ra)2, or any Rs and R7, together with the common nitrogen to which they are both attached, form an optionally substituted W-heteroaryl or an optionally substituted W-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyi, haloalkenyi, haioalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkeny!, optionally substituted aralkynyl, optionally substituted cycioalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclyialkyi, optionally substituted beterocyclyialkenyi, optionally substituted heterocyclyialkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroaryiaikenyi, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkyiene chain, an optionally substituted straight or branched aikenylene chain and an optionally substituted straight or branched alkynyiene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkyiene chain, an optionally substituted straight or branched aikenylene chain and an optionally substituted straight or branched alkynyiene chain; and each R11 is hydrogen, alkyl, cyano, nitro or -OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.
77. 98. A method of treating a disease or condition associated with Axl activity in a mammai, wherein the method comprises administering io the mammal a therapeutically effective amount of a compound of formula (I): wherein:

    R1, R4 and R8 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, -C(0)R8 and -C(0)N(R6)R7; R2 is aryl optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloaikyl, alkyl, cycioalkyi, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyi, optionally substituted heterocyclylalkenyi, -R9-OR6, -R9-G-R10-GR8, ~R9-0~R10-Q~R10-OR8, -R9~G~R10~CN, -R9-O-R10-C(O}OR8, -R9-G-R10-C(G)N(Re)R7, -R9-O-R10-S(O)pR8 (where p is 0,1 or 2), -R9-0-R10-N(R6)R7, -R9~G~R10~C(NRir)N(R11)H, -R9~GC(G)-R8, -R9-N(R6)R7, -R9-C(0)R8, -R9-C(Q)0R8, -R9-C(0)N(R®)R7, -R9-N(R6)C(0)0R8, -R9-N(R6)C(0)R8, -Rs-N(R6)S(G)iR8 (where t is 1 or 2), -R9-S(0),0R8 (where t is 1 or 2), -R9-S(0)pR8 (where p is 0, 1 or 2), and -R9-S(G),N(R6)R? (where t is 1 or 2); R3 is selected from the group consisting of aryi and heteroaryi, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloaikyl, alkyl, cycioalkyi, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryi, optionaliy substituted heteroarylaikyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted beterocyclylalkyl, optionally substituted heterocyclylalkenyl, -R9-OR8, ~R9-O-R10-OR8, -R9~Q~R10~Q~R10-GR8, -R9-O-R10-CN, -Rs-O-R10-C(G)ORs, -R9-O-R10-C(O)N(R6)R7, -R9-O"R10"S(O)pR8 (where p is 0, 1 or 2), -R9-O-R10-hJ(R6)R7, -Re-O-R10-C(NR11)N(R11)H, -R9-0C(0)-R8, -R9-N(R6)R7, -R9-G(0)R8, -R9~C(0)0R8, ~R9-C(0)N{Rs)R7, -R9-N(R6)C(0)0R8, -R9-!M(R6)C{G)R3, -R9-N(Re}S(0}tR8 (where t is 1 or 2), -R9-S(G)jOR8 (where t is 1 or 2), -R9--S{0}pR8 (where p is 0, 1 or 2), and -R9"S(0).N(R6)R7 (where t is 1 or 2); each R6 and R' is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyi, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloaIkylaIkyI, optionally substituted cycloalkylalkenyl, optionally substituted eycloalkylaikynyi, optionally substituted heterocyclyl, optionally substituted beterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted beterocyciylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, optionally substituted heteroarylaikenyl, optionally substituted heteroarylalkynyl, -R10-OR8, -R10~GN, ~R10-NO2, -R1Q~N(R8)2, -R10-C(O)OR8 and -R10~C(G)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted /V-heteroary! or an optionally substituted At-heterocyclyi; each R8 Is Independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted araikenyi, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycioaikylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted eycloalkylaikynyi, optionally substituted heterocyclyl, optionally substituted heterocyciylalkyi, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylaikynyi, optionally substituted heteroaryl, optionally substituted heteroarylaikyl, optionally substituted heteroarylaikenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched afkenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alky!, cyano, nitro or -OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof,
78. 99. The method of Claim 98 wherein the disease or condition is alleviated by the modulation of Axl activity.
79. 100. The method of Claim 98 wherein the disease of condition is alleviated by a increase in Axl activity.
80. 101. The method of Claim 98 wherein the disease of condition is alleviated by a decrease in Axl activity.
81. 102. The method of Claim 101 wherein the disease or condition is selected from the group consisting of rheumatoid arthritis, vascular disease, vascular injury, psoriasis, visual impairment due to macular degeneration, diabetic retinopathy, retinopathy of prematurity, kidney disease, osteoporosis, osteoarthritis and cataracts.
82. 103. The method of claim 101, wherein a manifestation of the disease or condition is solid tumor formation in said mammal.
83. 104. The method of Claim 103, wherein the disease or condition is selected from the group consisting of breast carcinoma, renai carcinoma, endometrial carcinoma, ovarian carcinoma, thyroid carcinoma, non-small cell lung carcinoma, melanoma, prostate carcinoma, sarcoma, gastric cancer and uveal melanoma.
84. 105. The method of claim 101, wherein a manifestation of the disease or condition is liquid tumor formation in said mammal.
85. 106. The method of ciaim 105, wherein the disease or condition is myeloid leukemia or lymphoma.
86. 107. The method of Ciaim 101 wherein the disease or condition is endometriosis.